Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
In Vivo
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
In Vivo

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Visit iiar on Facebook
  • Follow us on Linkedin
Research ArticleClinical Studies

C-Reactive Protein Gene Variants and Their Serum Levels in Early Adult-onset Type 2 Diabetes Mellitus

YU-CHUEN HUANG, CHING-CHU CHEN, TZU-YUAN WANG, HUNG TRAN THE NGUYEN, YUNG-HSIANG CHEN, CHIA-MING WU, YA-WEN CHANG, WEN-LING LIAO and FUU-JEN TSAI
In Vivo September 2019, 33 (5) 1685-1690; DOI: https://doi.org/10.21873/invivo.11656
YU-CHUEN HUANG
1School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
2Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
CHING-CHU CHEN
1School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
3Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TZU-YUAN WANG
3Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
HUNG TRAN THE NGUYEN
4International Master's Program of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YUNG-HSIANG CHEN
5Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
CHIA-MING WU
2Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YA-WEN CHANG
2Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
WEN-LING LIAO
5Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan, R.O.C.
6Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: d0704@www.cmuh.org.tw wl0129@mail.cmu.edu.tw
FUU-JEN TSAI
7Department of Medical Research, Medical Genetics and Pediatrics, China Medical University Hospital, Taichung, Taiwan, R.O.C.
8Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan, R.O.C.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: d0704@www.cmuh.org.tw wl0129@mail.cmu.edu.tw
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: C-Reactive protein (CRP) is a common marker of inflammation. Elevated CRP levels have been associated with increased risk of development of type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association of CRP gene polymorphisms with early-onset T2DM and the effect of genetic variants on CRP level. Materials and Methods: In total, 948 individuals with early-onset (n=271) or late-onset (n=677) T2DM were enrolled in the study. Five single-nucleotide polymorphisms (SNPs) in the CRP gene, namely rs3093077, rs2808630, rs1800947, rs11265263, and rs11265265, were selected for genotyping, and CRP levels were measured. Results: Genotypic, allelic, and haplotype frequencies of these five SNPs were not significantly different between patients with early- and those with late-onset. T2DM Higher serum CRP levels were independently associated with the C-allele of rs3093077 and T-allele of rs11265265 (p<0.001). Furthermore, the C-allele of rs3093077 was associated with higher CRP level in both early- (p=0.016) and late-onset (p<0.001) T2DM. Conclusion: CRP gene variants may contribute to the risk of early-onset T2DM by affecting the serum CRP level.

  • C-Reactive protein
  • polymorphism
  • early-onset
  • type 2 diabetes
  • Taiwan

Type 2 diabetes mellitus (T2DM) is currently a major public health concern worldwide (1). During the past two decades, the prevalence of T2DM in young adults has steadily increased (2-4). A major risk factor strongly associated with early-onset T2DM is obesity in children, adolescents and young adults (5-7). From extensive experimental, clinical, and epidemiological studies, obesity has been linked to activation of innate immunity-related inflammatory signaling pathways. Inflammatory cytokines, such as interleukin-6 (IL6) and tumor necrosis factor-alpha (TNFα), and acute-phase reactants such as C-reactive protein (CRP) can block major anabolic cascades downstream of insulin signaling, thereby disrupting insulin homeostasis and increasing the risk of T2DM (8, 9). Studies have shown that reduction of inflammation and the ensuing acute-phase reactant responses through exercise, medication, or nutrition improves insulin sensitivity and delays disease onset (8).

Current evidence indicates that the risk of developing T2DM is regulated by lifestyle and genetic factors. Heterogeneity in the genetic determinants of T2DM development has been identified by candidate gene and genome-wide association studies (GWAS) across multiple populations (10-13). The influence of innate immunity-related inflammation genes combined with various lifestyle factors may affect serum levels of cytokines and inflammatory markers, that may play a pivotal role in susceptibility to T2DM. Therefore, investigation of the association between variants of inflammation-related genes and the risk of T2DM may help develop better approaches for early detection and prevention.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Characteristics of patients with type 2 diabetes mellitus at entry, grouped by age of onset (early: <45 years; late: ≥45 years).

Recent evidence from linkage and GWAS studies has implicated a region of chromosome 1q21-23 encompassing the CRP gene with risk of T2DM development in various ethnic populations (14-16). CRP, a common marker of inflammation, is an acute-phase reactant regulated by cytokines, predominantly IL6 and TNFα. CRP plays a critical role in T2DM by its action on pancreatic β-cells and is thought to be an early risk factor for T2DM (17). In vitro studies have shown an association between the serum level of high-sensitivity CRP and β-cell dysfunction and insulin resistance (18, 19). Moreover, elevation of high-sensitivity CRP in diabetic patients has been associated with an increased risk of diabetic vasculopathy (18, 20-22). Furthermore, several single-nucleotide polymorphisms (SNPs) in the CRP gene have been reported to be associated with serum CRP level, insulin sensitivity, and T2DM incidence (23). Based on these observations, we investigated the association between variants of the CRP gene and early-onset T2DM in the Han Chinese population of Taiwan.

Materials and Methods

Patient and data collection. In total, 948 patients with T2DM (age >20 years) from the China Medical University Hospital in Taiwan were enrolled in the study, and informed consent was acquired from all patients. Diabetes was diagnosed based on the patient medical records and fasting plasma glucose level using the American Diabetes Association Criteria (24). Patients with type 1 diabetes, gestational diabetes, and maturity-onset diabetes of the young were excluded from this study. According to the age recommended by the American Diabetes Association for T2DM screening in adults, patients with type 2 diabetes were segregated into two subgroups: (i) early-onset diabetes (n=271; age at diagnosis, at least 20 years but less than 45 years) and (ii) late-onset diabetes (n=677; age at diagnosis, 45 years or more). Data regarding age, sex, duration of disease, weight, height, and circumference of waist and hip (waist-to-hip ratio) of each patient were obtained from questionnaires. Blood samples for genomic DNA isolation were collected by venipuncture, and serological tests, including fasting glucose, hemoglobin A1c, and CRP, were performed at the time of enrollment. The study was approved by the Medical Ethics Committee of the China Medical University Hospital, Taichung, Taiwan (approval number: CMUH103-REC2-071) and performed according to the tenets of the Declaration of Helsinki for research involving human subjects.

SNP selection and genotyping. Five SNPs of CRP gene rs3093077, rs2808630, rs1800947, rs11265263, and rs11265265 (positions: 159709846, 159711078, 159713648, 159740727, and 159743766 bp, respectively) were selected from the Illumina Hap550K chip (12), which has been used previously for GWAS in the Han Chinese population of Taiwan. SNPs were selected by applying the following criteria: (i) a threshold minor allelic frequency in the HapMap CHB population of 0.10 for tag SNPs; and (ii) a genotyping score ≥0.6, as recommended by the manufacturer (Illumina, Inc., San Diego, CA, USA) to ensure a high genotyping success rate. In order to avoid redundancy, markers with pairwise r2 correlations ≥0.8 for any selected marker were not genotyped. Deviation from the Hardy–Weinberg equilibrium was not observed for any SNP. For genotyping, all blood samples were de-identified prior to analysis, and only the project investigator had access to the link for individual identities. Laboratory personnel involved in genotyping were blinded to the age at diabetic onset of the study patients. Genomic DNA was extracted from peripheral blood leukocytes using Genomic DNA kit (Qiagen, Valencia, CA, USA), and genotyping was performed using an allele-specific extension and ligation assay (Illumina) according to the manufacturer's instructions.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

Genotypic and allelic frequencies of C-reactive protein (CRP) gene variants for patients with early and late-onset type 2 diabetes mellitus.

Statistical analyses. The distributions of genotypic and allelic frequencies of the polymorphisms in patients with early-onset (age <45 years) and late-onset (age ≥45 years) T2DM ware analyzed using the chi-squared or Fisher exact test for differences in proportions. Odds ratios (OR) were calculated for associations with genotypic and allelic frequencies with a 95% confidence interval (CI) using unconditional logistical regression. The effect of the CRP gene SNP genotype on serum CRP level was analyzed using a general linear regression model after logarithmic transformation of CRP data. All statistical analyses were conducted using IBM SPSS Statistics 22 (IBM Co., Armonk, NY, USA), and p-values of less than 0.05 (two-sided) were considered significant.

Results

In our database, 28.6% (n=271) of patients had early-onset T2DM (mean age at diagnosis=38.6±4.7 years), and 71.4% (n=677) had late-onset T2DM (mean age at diagnosis=54.47±6.4 years). Clinical and biomedical parameters of patients with early-onset and late-onset T2DM are compared in Table I. We recorded a higher number of men, younger individuals, longer disease duration, and lower percentage of those with an estimated glomerular filtration rate <60 ml/min/1.73 m2 in those with early-onset T2DM. None of the observed characteristics, including body mass index, waist-to-hip ratio, and serological marker levels (i.e. fasting glucose insulin, hemoglobin A1c, and CRP), in this study showed significant differences between these two groups. Furthermore, no significant differences in prevalence of diabetic retinopathy and albumin-to-creatinine ratio were observed.

In order to identify SNPs associated with early-onset T2DM, five SNPs within CRP were genotyped. The genotypic and allelic frequencies of these five polymorphisms were not significantly different between patients with early-onset and late-onset T2DM (Table II). Furthermore, we investigated the association between the CRP haplotype and susceptibility to early-onset T2DM, and no significant difference was found (Table III).

The effect of genotype on serum CRP level was also investigated (Table IV). A significant effect (both p<0.001) of the C-allele of SNP rs3093077 and T-allele of SNP rs11265265 on elevation of serum CRP level was observed in multivariate regression analysis after adjusting for gender, DM duration, and BMI. In addition, we stratified the patients with T2DM according to early- or late-onset, and the C-allele of rs3093077 was significantly associated with elevation of serum CRP level in both the early- and late-onset groups (p=0.016 and p<0.001, respectively). However, the T-allele of rs1126265 was only significantly associated with elevation of CRP level in the group with late-onset T2DM (p<0.001).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table III.

Haplotype analysis of gene encoding C-reactive protein (CRP).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table IV.

Effect of single nucleotide polymorphisms (SNPs) of the gene encoding C-reactive protein (CRP) on serum CRP level by genotype in serum from patients with type 2 diabetes mellitus (T2DM).

Discussion

Polymorphisms of several inflammation-related candidate genes such as those for toll-like receptor 4, ILα, IL6 and TNFα have been reported to contribute to T2DM (17, 25). However, only a few studies have examined the influence of genetics on age at T2DM diagnosis, and no high impact genes have been directly linked to T2DM onset. This study investigated five SNPs (rs3093077, rs2808630, rs1800947, rs11265263, and rs11265265) of the CRP gene and their association with early-onset T2DM. None of the selected SNPs were significantly associated with early-onset T2DM. It is possible that the SNPs examined in this study may not play important roles in T2DM development at an early age or might not capture all possible genetic variations in the CRP gene. Further studies exploring other CPR variants within this population, as well as experiments addressing genetic changes and their relationship to protein function, will help to identify the true causal variants of T2DM. In addition, the non-significant results of the association between the CRP gene and early-onset T2DM may be due to the sample size. Thus, the study may not have been sufficiently powered to detect a weak association between CRP genotype and early-onset T2DM.

Several SNPs, including rs1800947 (G1059C) (26-28), rs2794521 (A1009G) (29), rs3091244, and rs1205 (26), of CRP gene have been associated with concentrations of circulating CRP in patients of different ethnicities with different diseases. The relationship between CRP variants and serum CRP level was also explored in our T2DM study population. A significant genetic effect on serum CRP level was observed in this study. SNPs rs3093077 and rs11265265 were associated with CRP level in patients with T2DM. Among these SNPs, rs3093077 was previously reported to be associated with CRP level in different populations, including in Denmark (30), the Framingham Heart Study cohort in America (31), the United Kingdom (32), and Taiwan (33), but not in Italians (34). SNP rs3093077 is located in the 3’ flanking region of the CRP gene. It often contains a transcription unit to regulate formation of the 3’ end of the message and may also contain enhancers or other protein-binding sites. SNPs in this region of CRP have been shown to affect the serum CRP level (29).

Furthermore, studies have shown that obesity can influence CRP concentration by stimulating overexpression of cytokines such as IL6 and TNFα (26). In addition, the effect of gender on CRP level has been shown in previous studies. Sheu et al. found that the CRP rs2794521 GG genotype was associated with lower serum CRP concentrations in a group of elderly men (29). Hence, we adjusted for the effect of BMI and gender in a multivariate model, and the results showed that the serum CRP level was affected by the CRP gene independently. The results highlight the importance of the interplay between genetic and lifestyle factors in phenotypic development of complex traits.

Conclusion

In conclusion, this study provides evidence for the association of serum CRP level and CRP gene polymorphisms in patients with T2DM, although a significant association between polymorphisms of the CRP gene and age at T2DM diagnosis was not observed.

Acknowledgements

The Authors thank the National Center for Genome Medicine, Taipei, Taiwan for providing support services for data coordination, subject recruitment, and project management.

Grant support: This work was supported in part by research grants from China Medical University Hospital (DMR-107-056 and DMR-108-036), Taichung City, Taiwan; and from Academia Sinica (AS-BD-108-9), Taipei City, Taiwan.

Footnotes

  • Authors' Contributions

    FJ Tsai and WL Liao conceived and supervised all works; YC Huang and WL Liao designed, analyzed and drafted the article; CC Chen, TY Wang, TTH Nguyen, YH Chen, CM Wu, and YW Chang participated interpretation the data. All Authors read and approved the final article.

  • This article is freely accessible online.

  • Conflicts of Interest

    None of the Authors have any financial interests to disclose.

  • Received June 20, 2019.
  • Revision received July 9, 2019.
  • Accepted July 12, 2019.
  • Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Shaw JE,
    2. Sicree RA,
    3. Zimmet PZ
    : Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87(1): 4-14, 2010. PMID: 19896746. DOI: 10.1016/j.diabres.2009.10.007
    OpenUrlCrossRefPubMed
  2. ↵
    1. Koopman RJ,
    2. Mainous AG 3rd.,
    3. Diaz VA,
    4. Geesey ME
    : Changes in age at diagnosis of type 2 diabetes mellitus in the United States, 1988 to 2000. Ann Fam Med 3(1): 60-63, 2005. PMID: 15671192. DOI: 10.1370/afm.214
    OpenUrlAbstract/FREE Full Text
    1. Tseng CH,
    2. Tseng CP,
    3. Chong CK,
    4. Huang TP,
    5. Song YM,
    6. Chou CW,
    7. Lai SM,
    8. Tai TY,
    9. Cheng JC
    : Increasing incidence of diagnosed type 2 diabetes in Taiwan: Analysis of data from a national cohort. Diabetologia 49(8): 1755-1760, 2006. PMID: 16788802. DOI: 10.1007/s00125-006-0314-4
    OpenUrlCrossRefPubMed
  3. ↵
    1. Chang CH,
    2. Shau WY,
    3. Jiang YD,
    4. Li HY,
    5. Chang TJ,
    6. Sheu WH,
    7. Kwok CF,
    8. Ho LT,
    9. Chuang LM
    : Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999-2004: A National Health Insurance data set study. Diabet Med 27(6): 636-643, 2010. PMID: 20546280. DOI: 10.1111/j.1464-5491. 2010.03007.x
    OpenUrlCrossRefPubMed
  4. ↵
    1. Shield JP,
    2. Lynn R,
    3. Wan KC,
    4. Haines L,
    5. Barrett TG
    : Management and 1 year outcome for UK children with type 2 diabetes. Arch Dis Child 94(3): 206-209, 2009. PMID: 18838418. DOI: 10.1136/adc.2008.143313
    OpenUrlAbstract/FREE Full Text
    1. Hsia Y,
    2. Neubert AC,
    3. Rani F,
    4. Viner RM,
    5. Hindmarsh PC,
    6. Wong IC
    : An increase in the prevalence of type 1 and 2 diabetes in children and adolescents: Results from prescription data from a UK general practice database. Br J Clin Pharmacol 67(2): 242-249, 2009. PMID: 19260863. DOI: 10.1111/j.1365-2125.2008. 03347.x
    OpenUrlCrossRefPubMed
  5. ↵
    1. Liao WL,
    2. Chen CC,
    3. Chang CT,
    4. Wu JY,
    5. Chen CH,
    6. Huang YC,
    7. Tsai CH,
    8. Tsai FJ
    : Gene polymorphisms of adiponectin and leptin receptor are associated with early onset of type 2 diabetes mellitus in the Taiwanese population. Int J Obes 36(6): 790-796, 2012. PMID: 21931325. DOI: 10.1038/ijo.2011.174
    OpenUrl
  6. ↵
    1. Bassuk SS,
    2. Manson JE
    : Epidemiological evidence for the role of physical activity in reducing risk of type 2 diabetes and cardiovascular disease. J Appl Physiol 99(3): 1193-1204, 2005. PMID: 16103522. DOI: 10.1152/japplphysiol.00160.2005
    OpenUrlCrossRefPubMed
  7. ↵
    1. Sifnaios E,
    2. Mastorakos G,
    3. Psarra K,
    4. Panagopoulos ND,
    5. Panoulis K,
    6. Vitoratos N,
    7. Rizos D,
    8. Creatsas G
    : Gestational diabetes and T-cell (Th1/Th2/Th17/Treg) immune profile. In Vivo 33(1): 31-40, 2019. PMID: 30587599. DOI: 10.21873/invivo.11435
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. McCarthy MI,
    2. Zeggini E
    : Genome-wide association studies in type 2 diabetes. Curr Diab Rep 9(2): 164-171, 2009. PMID: 19323962. DOI: 10.1007/s11892-009-0027-4
    OpenUrlCrossRefPubMed
    1. Lango H,
    2. Palmer CN,
    3. Morris AD,
    4. Zeggini E,
    5. Hattersley AT,
    6. McCarthy MI,
    7. Frayling TM,
    8. Weedon MN
    : Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes 57(11): 3129-3135, 2008. PMID: 18591388. DOI: 10.2337/db08-0504
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Tsai FJ,
    2. Yang CF,
    3. Chen CC,
    4. Chuang LM,
    5. Lu CH,
    6. Chang CT,
    7. Wang TY,
    8. Chen RH,
    9. Shiu CF,
    10. Liu YM,
    11. Chang CC,
    12. Chen P,
    13. Chen CH,
    14. Fann CS,
    15. Chen YT,
    16. Wu JY
    : A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese. PLoS Genet 6(2): e1000847, 2010. PMID: 20174558. DOI: 10.1371/journal.pgen.1000847
    OpenUrlCrossRefPubMed
  10. ↵
    1. Liao WL,
    2. Tsai FJ
    : Personalized medicine in type 2 diabetes. Biomedicine 4: 8, 2014. PMID: 25520921. DOI: 10.7603/s40681-014-0008-z
    OpenUrl
  11. ↵
    1. Lu Q,
    2. Song Y,
    3. Wang X,
    4. Won S,
    5. Cui Y,
    6. Elston RC
    : The effect of multiple genetic variants in predicting the risk of type 2 diabetes. BMC Proc 3(Suppl 7): S49, 2009. PMID: 20018041. DOI: 10.1186/1753-6561-3-s7-s49
    OpenUrlCrossRefPubMed
    1. Xiang K,
    2. Wang Y,
    3. Zheng T,
    4. Jia W,
    5. Li J,
    6. Chen L,
    7. Shen K,
    8. Wu S,
    9. Lin X,
    10. Zhang G,
    11. Wang C,
    12. Wang S,
    13. Lu H,
    14. Fang Q,
    15. Shi Y,
    16. Zhang R,
    17. Xu J,
    18. Weng Q
    : Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the chinese: Significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24. Diabetes 53(1): 228-234, 2004. PMID: 14693720. DOI: 10.2337/diabetes.53.1.228
    OpenUrlAbstract/FREE Full Text
  12. ↵
    1. Ng MC,
    2. So WY,
    3. Cox NJ,
    4. Lam VK,
    5. Cockram CS,
    6. Critchley JA,
    7. Bell GI,
    8. Chan JC
    : Genome-wide scan for type 2 diabetes loci in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25. Diabetes 53(6): 1609-1613, 2004. PMID: 15161769. DOI: 10.2337/diabetes.53.6.1609
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Arora P,
    2. Garcia-Bailo B,
    3. Dastani Z,
    4. Brenner D,
    5. Villegas A,
    6. Malik S,
    7. Spector TD,
    8. Richards B,
    9. El-Sohemy A,
    10. Karmali M,
    11. Badawi A
    : Genetic polymorphisms of innate immunity-related inflammatory pathways and their association with factors related to type 2 diabetes. BMC Med Genet 12: 95, 2011. PMID: 21756351. DOI: 10.1186/1471-2350-12-95
    OpenUrlCrossRefPubMed
  14. ↵
    1. Pfutzner A,
    2. Standl E,
    3. Strotmann HJ,
    4. Schulze J,
    5. Hohberg C,
    6. Lubben G,
    7. Pahler S,
    8. Schondorf T,
    9. Forst T
    : Association of high-sensitive C-reactive protein with advanced stage beta-cell dysfunction and insulin resistance in patients with type 2 diabetes mellitus. Clin Chem Lab Med 44(5): 556-560, 2006. PMID: 16681424. DOI: 10.1515/cclm.2006.108
    OpenUrlPubMed
  15. ↵
    1. Chou HH,
    2. Hsu LA,
    3. Liu CJ,
    4. Teng MS,
    5. Wu S,
    6. Ko YL
    : Insulin resistance is associated with C-reactive protein independent of abdominal obesity in nondiabetic Taiwanese. Metabolism 59(6): 824-830, 2010. PMID: 20004425. DOI: 10.1016/j.metabol.2009.09.030
    OpenUrlCrossRefPubMed
  16. ↵
    1. Pfutzner A,
    2. Schondorf T,
    3. Hanefeld M,
    4. Forst T
    : High-sensitivity c-reactive protein predicts cardiovascular risk in diabetic and nondiabetic patients: Effects of insulin-sensitizing treatment with pioglitazone. J Diabetes Sci Technol 4(3): 706-716, 2010. PMID: 20513338. DOI: 10.1177/193229 68100040 0326
    OpenUrlCrossRefPubMed
    1. Anan F,
    2. Takahashi N,
    3. Nakagawa M,
    4. Ooie T,
    5. Saikawa T,
    6. Yoshimatsu H
    : High-sensitivity C-reactive protein is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients. Metabolism 54(4): 552-558, 2005. PMID: 15798966. DOI: 10.1016/j.metabol.2004.11.012
    OpenUrlCrossRefPubMed
  17. ↵
    1. Mugabo Y,
    2. Li L,
    3. Renier G
    : The connection between C-reactive protein (CRP) and diabetic vasculopathy. Focus on preclinical findings. Curr Diabetes Rev 6(1): 27-34, 2010. PMID: 20034371. DOI: 10.2174/157339910790442628.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Wolford JK,
    2. Gruber JD,
    3. Ossowski VM,
    4. Vozarova B,
    5. Antonio Tataranni P,
    6. Bogardus C,
    7. Hanson RL
    : A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians. Mol Genet Metab 78(2): 136-144, 2003. PMID: 12618085. DOI: 10.1016/S1096-7192(02)00230-5.
    OpenUrlCrossRefPubMed
  19. ↵
    Diagnosis and classification of diabetes mellitus. Diabetes Care 36(Suppl 1): S67-74, 2013. PMID: 23264425. DOI: 10.2337/dc13-S067
    OpenUrlFREE Full Text
  20. ↵
    1. Badawi A,
    2. Klip A,
    3. Haddad P,
    4. Cole DE,
    5. Bailo BG,
    6. El-Sohemy A,
    7. Karmali M
    : Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention. Diabetes Metab Syndr Obes 3: 173-186, 2010. PMID: 21437087. DOI: 10.2147/DMSO.S9089.
    OpenUrlPubMed
  21. ↵
    1. Teng MS,
    2. Hsu LA,
    3. Wu S,
    4. Chang HH,
    5. Chou HH,
    6. Ko YL
    : Association between c-reactive protein gene haplotypes and C-reactive protein levels in Taiwanese: Interaction with obesity. Atherosclerosis 204(2): e64-69, 2009. PMID: 19101671. DOI: 10.1016/j.atherosclerosis.2008.10.034
    OpenUrl
    1. Dai DF,
    2. Chiang FT,
    3. Lin JL,
    4. Huang LY,
    5. Chen CL,
    6. Chang CJ,
    7. Lai LP,
    8. Hsu KL,
    9. Tseng CD,
    10. Tseng YZ,
    11. Hwang JJ
    : Human C-reactive protein (CRP) gene 1059g>c polymorphism is associated with plasma CRP concentration in patients receiving coronary angiography. J Formos Med Assoc 106(5): 347-354, 2007. PMID: 17561469. DOI: 10.1016/s0929-6646(09)60319-3
    OpenUrlPubMed
  22. ↵
    1. Thalmaier D,
    2. Dambacher J,
    3. Seiderer J,
    4. Konrad A,
    5. Schachinger V,
    6. Pfennig S,
    7. Otte JM,
    8. Crispin A,
    9. Goke B,
    10. Ochsenkuhn T,
    11. Lohse P,
    12. Brand S
    : The +1059G/C polymorphism in the C-reactive protein (CRP) gene is associated with involvement of the terminal ileum and decreased serum crp levels in patients with crohn's disease. Aliment Pharmacol Ther 24(7): 1105-1115, 2006. PMID: 16984505. DOI: 10.1111/j.1365-2036.2006. 03093.x
    OpenUrlPubMed
  23. ↵
    1. Sheu WH,
    2. Chen YD,
    3. Yu CY,
    4. Guo X,
    5. Lee TC,
    6. Lee WJ,
    7. Chen YT,
    8. Rotter JI
    : C-reactive protein gene polymorphism 1009A>G is associated with serum CRP levels in Chinese men: A TCVGHAGE study. Clin Chim Acta 382(1-2): 117-123, 2007. PMID: 17511977. DOI: 10.1016/j.cca.2007.04.013
    OpenUrlCrossRefPubMed
  24. ↵
    1. Zacho J,
    2. Tybjaerg-Hansen A,
    3. Jensen JS,
    4. Grande P,
    5. Sillesen H,
    6. Nordestgaard BG
    : Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med 359(18): 1897-1908, 2008. PMID: 18971492. DOI: 10.1056/NEJMoa0707402
    OpenUrlCrossRefPubMed
  25. ↵
    1. Kathiresan S,
    2. Larson MG,
    3. Vasan RS,
    4. Guo CY,
    5. Gona P,
    6. Keaney JF Jr..,
    7. Wilson PW,
    8. Newton-Cheh C,
    9. Musone SL,
    10. Camargo AL,
    11. Drake JA,
    12. Levy D,
    13. O'Donnell CJ,
    14. Hirschhorn JN,
    15. Benjamin EJ
    : Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to interindividual variability in serum c-reactive protein level. Circulation 113(11): 1415-1423, 2006. PMID: 16534007. DOI: 10.1161/circulationaha.105.591271
    OpenUrlAbstract/FREE Full Text
  26. ↵
    1. Brunner EJ,
    2. Kivimaki M,
    3. Witte DR,
    4. Lawlor DA,
    5. Davey Smith G,
    6. Cooper JA,
    7. Miller M,
    8. Lowe GD,
    9. Rumley A,
    10. Casas JP,
    11. Shah T,
    12. Humphries SE,
    13. Hingorani AD,
    14. Marmot MG,
    15. Timpson NJ,
    16. Kumari M
    : Inflammation, insulin resistance, and diabetes--mendelian randomization using CRP haplotypes points upstream. PLoS Med 5(8): e155, 2008. PMID: 18700811. DOI: 10.1371/journal.pmed.0050155
    OpenUrlCrossRefPubMed
  27. ↵
    1. Huang CC,
    2. Chung CM,
    3. Leu HB,
    4. Lin TH,
    5. Hung SI,
    6. Wu TC,
    7. Huang PH,
    8. Lin SJ,
    9. Pan WH,
    10. Chen JW
    : Genetic variation in C-reactive protein in ethnic Chinese population in Taiwan. Eur J Clin Invest 43(5): 449-456, 2013. PMID: 23496329. DOI: 10.1111/eci.12067
    OpenUrl
  28. ↵
    1. Ottaviani S,
    2. Gorrini M,
    3. Scabini R,
    4. Kadija Z,
    5. Paracchini E,
    6. Mariani F,
    7. Ferrarotti I,
    8. Luisetti M
    : C-Reactive protein and alpha1-antitrypsin: Relationship between levels and gene variants. Transl Res 157(6): 332-338, 2011. PMID: 21575917. DOI: 10.1016/j.trsl.2010.12.014
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

In Vivo: 33 (5)
In Vivo
Vol. 33, Issue 5
September-October 2019
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on In Vivo.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
C-Reactive Protein Gene Variants and Their Serum Levels in Early Adult-onset Type 2 Diabetes Mellitus
(Your Name) has sent you a message from In Vivo
(Your Name) thought you would like to see the In Vivo web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
18 + 2 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
C-Reactive Protein Gene Variants and Their Serum Levels in Early Adult-onset Type 2 Diabetes Mellitus
YU-CHUEN HUANG, CHING-CHU CHEN, TZU-YUAN WANG, HUNG TRAN THE NGUYEN, YUNG-HSIANG CHEN, CHIA-MING WU, YA-WEN CHANG, WEN-LING LIAO, FUU-JEN TSAI
In Vivo Sep 2019, 33 (5) 1685-1690; DOI: 10.21873/invivo.11656

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
C-Reactive Protein Gene Variants and Their Serum Levels in Early Adult-onset Type 2 Diabetes Mellitus
YU-CHUEN HUANG, CHING-CHU CHEN, TZU-YUAN WANG, HUNG TRAN THE NGUYEN, YUNG-HSIANG CHEN, CHIA-MING WU, YA-WEN CHANG, WEN-LING LIAO, FUU-JEN TSAI
In Vivo Sep 2019, 33 (5) 1685-1690; DOI: 10.21873/invivo.11656
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Conclusion
    • Acknowledgements
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Treatment of Renal Anemia in Patients With Hemodialysis Using Hypoxia-inducible Factor (HIF) Stabilizer, Roxadustat: A Short-term Clinical Study
  • Pediatric Patients With Sickle Cell Disease at a Public Hospital: Nutrition, Compliance and Early Experience With L-Glutamine Therapy
  • Five-year Follow-up of Patients With Head and Neck Cancer Treated With Nivolumab and Long-term Responders for Over Two Years
Show more Clinical Studies

Similar Articles

Keywords

  • C-reactive protein
  • polymorphism
  • early-onset
  • type 2 diabetes
  • Taiwan
In Vivo

© 2022 In Vivo

Powered by HighWire