Research ArticleExperimental Studies
Open Access

Frequency and Diagnostic Utility of the −13910C>T MCM6 Gene Polymorphism for Lactose Intolerance in a Brazilian Northeast Population

GUILHERME PASSOS DE MORAIS, ANDRÉ PONTES THÉ, BEATRIZ MARIA DIAS NOGUEIRA, DEIVIDE DE SOUSA OLIVEIRA, LEIDIVAN SOUSA DA CUNHA, JEAN BRENO SILVEIRA DA SILVA, PATRÍCIA MARIA PONTES THÉ, ALEXANDRE DE ALMEIDA MONTEIRO, LUIS GONZAGA MOURA XAVIER, MARIA ELISABETE AMARAL DE MORAES and CAROLINE AQUINO MOREIRA-NUNES
In Vivo January 2026, 40 (1) 178-190; DOI: https://doi.org/10.21873/invivo.14183

Abstract

Background/Aim: Lactose intolerance (LI) is a common clinical condition associated with reduced lactase enzyme activity. The oral lactose tolerance test (OLTT), although widely used for diagnosis, has several limitations such as fasting, multiple blood collections, and gastrointestinal discomfort. As an alternative, genetic testing targeting the −13910C>T polymorphism in the MCM6 gene, a regulator of lactase expression, has gained prominence as it is non-invasive, rapid, and unaffected by physiological variation. This study aimed to evaluate the frequency of the −13910C>T polymorphism of the MCM6 gene in the population of Fortaleza and compare the genotyping results with the OLTT, to verify its diagnostic applicability.

Materials and Methods: A descriptive study was conducted with data from 2359 patients examined between January 2022 and May 2025 at a private laboratory. Concordance between genotyping and OLTT was analyzed in 24 patients who underwent both tests, with OLTT considered the reference standard. Sensitivity, specificity, accuracy, and Kappa coefficient were calculated. All analyses were performed using R software.

Results: The median age of participants was 7 years (range=0.06-100 years). The observed genotype frequencies were 52.90% for the CC genotype, 38.74% for CT, and 8.35% for TT. The Kappa test demonstrated moderate agreement between the genetic test and OLTT [k=0.583 (p=0.00413)], with a sensitivity of 81.82% [95% confidence interval (CI)=48.22-97.71], overall accuracy of 79.17%, and specificity of 76.92% (95%CI=48.16-94.96).

Conclusion: Genotyping for the −13910C>T polymorphism in the MCM6 gene represents a promising diagnostic alternative for lactose intolerance, offering a feasible and less invasive approach with good sensitivity and specificity.

Keywords:

Introduction

Lactose intolerance (LI), also known as hypolactasia, is a common clinical condition characterized by reduced or absent activity of the enzyme lactase-phlorizin hydrolase (LPH) (EC 3.2.1.108-EC 3.2.1.62), which is essential for the metabolism of lactose in humans (1). This enzyme, expressed exclusively in the brush border of small intestinal enterocytes, is responsible for the hydrolysis of lactose into glucose and galactose. In LPH deficiency, undigested lactose reaches the colon, where it is fermented by the intestinal microbiota, resulting in the production of gases such as hydrogen (H2), carbon dioxide (CO2), methane (CH4), and other organic metabolites. This fermentation process leads to the characteristic clinical manifestations of the condition, such as abdominal pain, flatulence, diarrhea, and other gastrointestinal complaints (1, 2).

Given the central role of LPH in lactose metabolism, its expression pattern throughout life has important clinical implications. LPH activity is typically high during infancy, ensuring adequate digestion of lactose in breast milk, but generally decreases after weaning, a process known as lactase non-persistence (LNP) (3). Epidemiological studies estimate that approximately 65-75% of the global population exhibits some degree of lactose maldigestion, with an even higher prevalence among individuals of African, Asian, and indigenous descent (4-6).

Traditionally, the diagnosis of LI has been based on phenotypic tests, such as the oral lactose tolerance test (OLTT) and the breath hydrogen test (BHT). Although widely used, these methods have limitations: they require prolonged fasting, forced lactose intake, multiple sample collections, and are influenced by comorbidities (such as diabetes and gastrointestinal disorders) and the intestinal microbiota. These limitations render functional tests less suitable in young children, the elderly, patients with diabetes, or in clinical situations where the discomfort or risk associated with the test renders its performance unfeasible (7-10).

Genetic testing has emerged as a reliable approach for assessing the genetic predisposition to LI in recent years. The −13910C>T (rs4988235) polymorphism, located in the intron of the MCM6 gene, is currently the most investigated and widely validated marker for determining lactase persistence (LP) and NLP phenotypes in adults. Individuals homozygous for the C allele (CC) are predisposed to the LNP phenotype, associated with primary hypolactasia. In contrast, carriers of the T allele (CT or TT) tend to express the LP phenotype, maintaining persistent enzymatic activity throughout life (11-13).

In Brazil, a country with a highly admixed population, the genetic landscape becomes more complex. The prevalence of LNP varies significantly according to the predominant ancestry in each region. While the −13910C>T polymorphism is the main predictor in individuals of European ancestry, other variants associated with LP are found in populations of African origin. This genetic heterogeneity poses a significant diagnostic challenge and reinforces the need for regional population studies (6, 14).

In view of this background, the present study aimed to estimate the frequency of the −13910C>T (rs4988235) polymorphism in a population in Northeast Brazil; compare the results of genotyping with OLTT, evaluating the agreement between the methods; and discuss the clinical and population applicability of genetic testing as a diagnostic alternative for LI.

Materials and Methods

Design and study population. A cross-sectional, single-center study was undertaken with data from patients seen between January 2022 and May 2025 at a private laboratory in Fortaleza, Ceará, Brazil. The study included patients who underwent investigation of lactose intolerance using the OLTT and/or molecular analysis of the MCM6 gene polymorphism −13910 C>T (rs4988235).

A total of 15,763 patients of both sexes and across different age groups were included in the study. For comparative purposes, participants were stratified into three groups: Group E, comprising individuals who underwent only the enzymatic test; Group G, consisting of those who underwent only the genetic test; and Group EG, encompassing patients who underwent both diagnostic assessments.

The genotypic frequencies obtained were compared to the frequencies recorded in international public databases, from the ALFA (Allele Frequency Aggregator) database, maintained by the NCBI, for different ethnic groups (Europeans, Africans, Asians, Latin Americans).

Ethical issues. This study was a survey of data from the laboratory’s clinical databases that was performed without recruiting or identifying patients. It was submitted to the Research Ethics Committee of the Christus University Center-UNICHRISTUS and approved under opinion no. 6.738.481 (CAAE: 78062424.2.0000.5049).

Biological samples. Peripheral whole blood samples were used for both diagnostic tests. Only samples collected in tubes containing EDTA as an anticoagulant were accepted for the genetic test to prevent interference with the results of the molecular analyses. All samples were collected to meet the routine diagnostic demand of clients at the clinical laboratory for lactose intolerance testing; therefore, no additional blood collections were required. According to standard methods, 5 ml of blood was collected in tubes containing EDTA for molecular analysis and in sodium fluoride tubes for biochemical analysis.

Oral Lactose Tolerance Test (OLTT). Assessment of lactose intolerance was assessed using the OLTT, according to a standardized clinical protocol and based on the enzymatic glucose dosage methodology described in the package insert for the GLUCOSE OSR6X21 kit (Beckman Coulter Inc.®, Brea, CA, USA). Before performing the test, participants were instructed to fast for a period of 8 to 14 h, and to avoid intense physical activity and alcohol consumption in the previous 24 h.

The samples were collected in tubes containing sodium fluoride to inhibit glycolysis and preserve the concentration of circulating glucose. After proper identification, samples were processed immediately or stored in refrigerators between 2°C and 8°C for a maximum of two h until analysis. Afterwards, the participants ingested a standardized solution containing 75 g of lactose dissolved in 300 ml of water. After ingesting the lactose, venous blood samples were taken at 30-, 60-, 90- and 120-min. Collection, handling, storage and identification of all samples was identical.

The quantification of glucose was carried out using an automated spectrophotometric method based on a liquid-phase enzymatic reaction involving hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6P-DH). Using this system, the glucose in the sample is initially phosphorylated by HK in the presence of ATP and magnesium ions, giving rise to glucose-6-phosphate and ADP. Next, glucose-6-phosphate is specifically oxidized by G6P-DH, with concomitant reduction of the cofactor NAD+ to NADH. NAD formation is monitored by reading the absorbance at 340 nm, which is directly proportional to the concentration of glucose present in the sample analyzed.

The glycemic curve was interpreted based on widely established criteria. The absence of a significant glycemic response after administration of the oral lactose load, defined as an increase of less than 20 mg/dl in relation to the baseline value, was considered suggestive of LI. However, rises of 20 mg/dl or more at any point on the curve were interpreted as indicating adequate digestion and absorption of lactose, reflecting functional activity of the lactase enzyme.

Extraction, quantification and DNA purity analysis. To perform the molecular analyses, the peripheral whole blood samples were subjected to the DNA extraction process using the TANBead OptiPure Blood DNA Auto Kit (TANBead®, Taoyuan, Taiwan, ROC). The extraction kit consists of tubes pre-arranged in strips for automated. Each strip is designed for the extraction of a single sample and has six tubes containing lysis buffer, magnetic beads, washing solutions and elution buffer.

After identification, a volume of 10 μl of proteinase K was added to the first automatic tube of each strip. The whole blood samples were then slightly homogenized by inversion and 300 μl of biological sample was also added to the first tube. The strips were placed on a rack and inserted in the Maelstrom 4800 automated extraction equipment (TANBead). The equipment was programmed to run program 61E, according to the manufacturer’s recommendations for DNA extractions with the TANBead® Blood kit.

Once the extraction process was complete, the eluted material was recovered and approximately 80 μl were transferred to previously identified 1.5 ml microtubes. To examine the quality of the extracted material, the quantification and purity parameters were analyzed using a NanoDrop spectrophotometer (NanoDrop Technologies, Wilmington, DE, USA). A minimum concentration of 10 ng/μl of DNA per purified sample was set as a criterion for sample acceptability, as well as a 260/280 ratio between 1.8 and 1.9 and a 260/230 ratio between 1.8 and 2.2.

Molecular analysis. Molecular analyses were carried out with 5 μl of purified DNA and real-time PCR, using the Lactose Intolerance REAL-TIME PCR Genotyping Kit (DNA Technology, Moscow, Russia), designed to discriminate the genotypes of the MCM6:13910 C>T polymorphism associated with adult-type hypolactasia. The quantitative real-time PCR (qPCR) reaction and execution procedure was carried out according to the recommendations provided by the diagnostic kit manufacturer.

The DT-prime 5 equipment (DNA Technology) perform the PCR with the following thermocycling steps: step one, one cycle starting at 80°C for 2 min and ending at 94°C for 5 min; step two, five cycles at 94°C for 30 s and 67°C for 15 s; step three, 45 cycles at 94°C for 5 s and 67°C for 15 s; step four, with one cycle at 25°C for 30 s; step five, 50 cycles at 25°C for 15 s.

All reactions were based on the melting curve principle using specific primers and probes for the detection of the C and T alleles. The FAM fluorophore was used as a marker for the C allele, the wild-type allele associated with non-persistence of lactase, while the HEX fluorophore was used for the T allele, the mutant allele associated with persistence of lactase. In addition, probes labeled with the Cy5 fluorophore were used to detect human genomic DNA as an endogenous control for the reaction.

Data analysis was based on the evaluation of the melting temperature (Tm) for each of the alleles. The genotypes were discriminated as homozygous wild-type (C/C) when the Tm was 56.7°C for FAM and 47°C for HEX, homozygous mutant (T/T) when the Tm was 48.6°C for FAM and 56.7°C for HEX, and heterozygous (C/T) when the Tm was 56.4°C for FAM and 55.6°C for HEX.

Statistical analysis. Categorical variables are expressed as absolute and relative frequencies, while the continuous variables, such as age, are expressed as the median and their extreme values (minimum and maximum). Age comparisons between the groups were carried out using the non-parametric Kruskal-Wallis test. The chi-squared test was used to analyze sex distribution. The normality of the data was assessed using the Anderson-Darling test. Genotype distribution of the rs4988235 variant was assessed for Hardy-Weinberg Equilibrium (HWE) using the chi-squared (χ2) test, calculating allele frequencies (p and q) from the proportions observed for the locus.

Diagnostic performance of the genetic test was assessed in relation to the OLTT (considered the phenotypic standard), by estimating sensitivity, specificity, accuracy, positive predictive value and negative predictive value. Agreement between the methods was measured by Cohen’s kappa coefficient, whose interpretation followed the criteria proposed by Landis and Koch. All statistical analyses were carried out using the R software (version 4.5.1; R Core Team, Viena, Austria), a significance level (p <0.05) was adopted in all tests.

Results

The study population in Group E (n=13,404) had a median age of 37 years (range=2-96 years). Regarding sex distribution, 67.9% (n=9,101) were female and 32.1% (n=4,303) were male. Among these individuals, 60.5% (n=8,115) tested positive for lactose intolerance, whereas 39.5% (n=5,289) were classified as tolerant. The OLTT findings reflect the phenotypic manifestation of adult-type hypolactasia during the active digestive phase.

Group G (n=2,359) had a median age of 7 years (range=0.06–100 years). With respect to sex distribution, 43.0% (n=1,014) were male and 57.0% (n=1,345) were female. Group EG (n=24) had a median age of 33 years (range=3-86 years). Of these, 62.5% (n=15) were female and 37.5% (n=9) were male.

Comparative analysis of the demographic characteristics among the groups revealed statistically significant differences. The median age was significantly different among groups E, G, and EG, as assessed by the Kruskal-Wallis test (p<0.001). Likewise, the sex distribution also varied significantly among the groups, according to the χ2 (p <0.001). The demographic characteristics of all the patients in the study are summarized in Table I.

View this table:
Table I.

Demographic characteristics of the patients included in the study.

Figure 1 shows the six-month frequency of requests for the two tests between January 2022 and May 2025. Although both tests were carried out continuously throughout the period, there are significant variations in the number of tests applied, especially the OLTT, which is still used at a higher frequency when compared to the genetic test.

Figure 1.
Figure 1.

Six-month frequency of diagnostic tests for lactose intolerance. Line graph comparing the frequency of requests for the Oral Lactose Tolerance Test (OLTT), represented by the blue line, and the genetic test, represented by the orange line, from January 2022 to May 2025. Data are expressed as absolute values (total number of requests), indicated at the points on each curve for the corresponding six-month period.

The genotypic distribution of Group G was assessed using Hardy-Weinberg equilibrium. The observed genotypes were compared to the expected values under the equilibrium assumption, resulting in a χ2 value=2.5983 and a p-value=0.1070. Therefore, no statistically significant deviation was observed, indicating that the study population maintains a genotypic distribution compatible with a population in equilibrium (Figure 2).

Figure 2.
Figure 2.

Comparison of Observed and Expected Genotype Frequencies under Hardy-Weinberg Equilibrium. The curves illustrate the theoretical distribution of genotype frequencies for a biallelic polymorphism (rs4988235) across the full range of allele frequencies. The blue line represents the TT genotype, the green line represents the heterozygous CT genotype, and the orange line represents the CC genotype. Plotted points show the comparison between expected (circles) and observed (triangles) frequencies in the studied population, calculated at an allele frequency of p=0.2772. All data are expressed as relative frequencies.

The estimated allele frequencies were 27.72% for the T allele (p=0.2772) and 72.28% for the C allele (q=0.7228). The genotypic distribution of the rs4988235 variant in our study was TT: 8.35%, CT: 38.74% and CC: 52.90% (Table II). The genotype frequencies were compared with data from the Allele Frequency Aggregator (ALFA) database, available at NCBI dbSNP (15), which gathers genetic information on this variant from different population groups.

View this table:
Table II.

Genotypic frequencies and Hardy-Weinberg Equilibrium analysis (HWE).

A comparison showed a wide interpopulation variation in the frequencies of this polymorphism, reflecting different historical and evolutionary patterns of consumption and adaptation to lactose. European populations, for example, showed a more balanced distribution between the three genotypes, with a high frequency of heterozygotes (CT=41.12%) and the TT genotype (36.09%), indicative of a higher prevalence of lactase persistence (LP). In contrast, African and Asian populations showed a marked predominance of the CC genotype (>75%), suggesting low lactose tolerance in these regions.

Figure 3 shows the distribution of the rs4988235 polymorphism genotypes. The comparison shows important variations between the population in our study and population groups from other parts of the world, revealing distinct genetic patterns in terms of probable IL.

Figure 3.
Figure 3.

Distribution of rs4988235 polymorphism genotypes in the population. This figure compares the population from Fortaleza, Ceará, Brazil, with global reference groups. The data are expressed as relative frequencies (%). Each stacked bar represents the proportional distribution of the CC, CT, and TT genotypes within a specific population. A higher frequency of the TT genotype is observed in the European population (36.09%), while the CC genotype is predominant in the African (77.39%) and Asian (91.47%) populations.

In comparison, the population of Fortaleza showed a frequency intermediate between the African and European populations, being closer to the profiles observed in Latin American 1 (individuals with Afro-Caribbean ancestry) and Latin American 2 (individuals with mostly European and Native American Ancestry), which also showed a higher frequency of individuals with the CC genotype and a lower proportion of TT. These findings corroborate the mixed-race nature of the Brazilian population and reinforce the importance of regional studies to understand the distribution of alleles related to lactose tolerance.

To assess the diagnostic concordance of the genetic test and the phenotype observed by OLTT, we conducted performance validation analyses. The genetic test showed a sensitivity of 81.82% [95% confidence interval (CI)=48.22-97.71], indicating a good ability to correctly identify positive cases. Specificity was 76.92% (95%CI=48.16-94.96), revealing that the test also has moderate performance in identifying negative cases. The results of the evaluation of the genetic test in comparison with OLTT are summarized in Table III.

View this table:
Table III.

Diagnostic performance of the genetic test compared with the Oral Lactose Tolerance Test (OLTT) as the reference standard.

Agreement between the molecular test for the rs4988235 polymorphism and the phenotypic classification based on OLTT was assessed using Cohen’s kappa coefficient, which demonstrated moderate concordance (k=0.583; p=0.00413). Regarding the diagnostic performance of the genetic assay, nine cases were classified as true positives, indicating concordant identification of LI by both methods, while 10 cases were considered true negatives, demonstrating consistent absence of LI. Conversely, three individuals were classified as false positives, in whom the presence of the polymorphism was not corroborated by the OLTT. Additionally, two false negatives were identified–patients whose OLTT confirmed LI despite absence of the polymorphism (Figure 4).

Figure 4.
Figure 4.

Concordance matrix for lactose intolerance diagnosis between a genetic test and the Oral Lactose Tolerance Test (OLTT). The matrix displays the cross-tabulation of results from the two methods. Data are expressed as absolute frequencies (number of individuals). Each box represents the count of individuals for a specific combination of test outcomes, with color intensity corresponding to the frequency. For both tests, a result of ‘1’ represents a positive test and ‘0’ represents a negative test.

Discussion

LI has a strong genetic basis and its prevalence varies globally due to different evolutionary pressures (1, 6, 14). This study characterized the genetic and phenotypic profile of LI in a regional cohort, revealing a frequency of 52.90% for the CC genotype (rs4988235), which is associated with NLP. This result, combined with the tests’ diagnostic performance, reflects the complex ancestral background of the Brazilian population and supports optimizing clinical diagnosis in this context.

Demographic analysis of the groups showed significant differences in how both tests were requested. Group G was significantly younger than the other groups, with a marked predominance of pediatric participants (median age of 7 years). Genetic testing for the C/T-13910 polymorphism in the LCT gene is an established method for predicting LP in adult populations. However, its application in children under six has significant limitations. This limitation arises from ontogenetic variability in lactase enzyme expression during the first years of life, which can lead to a discrepancy between genotype and the actual ability to digest lactose (16, 17).

In contrast, Group E was predominantly composed of adults, with a median age of 37 years. Although genetic testing is more practical, OLTT was the most requested test until May 2025 (Figure 1). This disparity likely reflects the greater clinical tradition and initially lower cost of OLTT. However, despite its historical use, the OLTT presents significant drawbacks. Its diagnostic accuracy is limited by low sensitivity and specificity, as its results can be influenced by gastric emptying, diet, and comorbid gastrointestinal conditions. In addition, it requires ingestion of a high lactose dose, often inducing significant gastrointestinal discomfort that reduces its acceptability, especially in pediatric populations (18, 19).

LP is a widely studied trait with well-described population genetic variations, although this understanding is not yet complete. LP is considered the wild-type trait and is closely linked to specific mutations in a cis-regulatory element in the MCM6 transcriptional enhancer, which regulates LCT gene expression. Among the identified variants, −13910:C>T (rs4988235) and −13495:C>T (rs4954490) are more prevalent in some parts of Europe, while others, such as −13907:C>G (rs41525747), −13915:T>G (rs41380347), −14009:T>G (rs869051967), and −14010:G>C (rs145946881) are found at varying frequencies in the Middle East and Africa (11, 20, 21).

We found that most individuals in our study carried at least one C allele (72.28%), suggesting a high prevalence of the NLP phenotype or partial lactose tolerance. Other population studies have established a clear link between the frequency of the T allele and European ancestry in different populations across the Americas. Populations with high European ancestry, such as those in Uruguay and Cuba, have T allele frequencies of 65% and 53%, respectively, while populations of African descent and Peruvian populations have frequencies below 10% (22, 23).

Supporting these findings, Flores et al. showed that the CC genotype is associated with a greater proportion of Indigenous ancestry in Latin American populations, while the CT and TT genotypes are more common among those with greater European ancestry (24). These data reinforce the hypothesis that the current distribution of the rs4988235 variant in the Americas can be largely explained by the contribution of founder populations and shows no consistent evidence of recent natural selection.

The genetic analysis of Group G for conformity with HWE (p=0.1070) indicated that the study population was in Hardy-Weinberg equilibrium and validates the samples for population studies. The HWE test is a crucial tool in population genetics (25, 26), and previous regional population studies have also reported HWE for this locus. In a study of a Swedish pediatric cohort, Almon et al. found that the −13910:C>T polymorphism in the LCT gene was in HWE in the Caucasian subpopulation (27).

A study by Manco et al. also found genotypic distributions consistent with HWE in a Portuguese cohort, with reported frequencies of 35.8% for CC, 48.1% for CT, and 16.1% for TT (28). These findings demonstrate that, despite variations in allele frequencies, the Hardy-Weinberg equilibrium holds even in admixed populations like that represented in our cohort.

A comparison of the genetic test for the rs4988235 polymorphism and the OLTT showed moderate agreement (k=0.583), indicating significant residual discrepancies between the results. Similarly, previous studies in Brazilian and Danish populations showed moderate agreement between both tests (k=0.420; k=0.559) (14, 29). The similarity in agreement indices reported in different populations suggests that such limitations are not specific to a single region but reflect inherent characteristics of the methods themselves.

Despite the advantages of genetic testing, the present study recognizes some important limitations. The main one is the small number of individuals (n=24) who underwent both tests, which constrains the analysis of sensitivity, specificity, and agreement. However, our results corroborate the findings of Araujo et al., which reported a sensitivity and specificity of 86% and 82.5%, respectively, in patients with metabolic syndrome, suggesting promising clinical utility (30).

Similarly, a study comparing different diagnostic methodologies for LI demonstrated good performance of genetic testing compared to OLTT, with a sensitivity of 87.5% and specificity of 92.7%. However, the agreement between OLTT and BHT was only moderate (k=0.530) (31). In pediatric patients, there was good agreement between genetic testing and BHT (k=0.675) (32). These findings reinforce that although functional tests are still useful, their performance is susceptible to physiological changes, comorbidities, and individual variability, justifying the growing preference for more stable and objective genetic methods.

A further limitation was the evaluation of only a single polymorphism, rs4988235. Although it is the most established marker for LP, the analysis did not include other functional polymorphisms. Relying solely on rs4988235 may underestimate LP and explain discrepancies with phenotypic tests, especially in admixed populations like the Brazilian one, suggesting that the inclusion of other polymorphisms could improve diagnostic concordance (14, 20).

Finally, the lack of additional clinical data limited more in-depth analyses of the clinical-genetic profile, which could have enriched the interpretation of the findings. Nevertheless, molecular testing based on the −13910C>T polymorphism is technically feasible, clinically useful, and potentially more cost-effective in various settings.

Conclusion

This study demonstrated that the population of Fortaleza has a high frequency of the CC genotype (−13910C>T) in the MCM6 gene, which is associated with NLP. The genetic test showed moderate agreement with the OLTT, along with good sensitivity and specificity, reinforcing its relevance as a diagnostic tool. These results highlight the importance of genotyping in diverse population contexts and suggest that molecular testing is a viable alternative, especially in patients with contraindications to OLTT or in age groups where its application is challenging. Finally, future investigations should prioritize larger, multicenter cohorts that include different genetic variants associated with lactase regulation, allowing for a better understanding of Brazilian population heterogeneity.

Footnotes

  • Authors’ Contributions

    Conceptualization, Morais GP, Thé AP, Moreira-Nunes CA; Provision of data and sub-sequent analysis interpretation, Morais GP, Thé AP, Oliveira DS, Thé PMP, Monteiro AM, Xavier LGM, da Silva JBS, Moraes MEAM, Moreira-Nunes CA; Writing-original draft preparation, Morais GP, Thé AP; Writing-review and editing, Nogueira, BMD, Oliveira DS, da Cunha LS., Moreira-Nunes CA; Funding acquisition, Moreira-Nunes CA. All Authors have read and agreed to the published version of the manuscript.

  • Conflicts of Interest

    The Authors declare no conflicts of interest in relation to this study. The funders had no role in the design of the study; in the collection, analyses, or data interpretation; in the writing of the manuscript, or in the decision to publish the results.

  • Funding

    This study was supported by Brazilian funding agencies: Coordination for the Improvement of Higher Education Personnel (CAPES, to Nogueira BMD, da Cunha LS), National Council of Technological and Scientific Development (Productivity in research scholarships to M.O.d.M.F, and CAM-N), Cearense Foundation of Scientific and Technological Support (FUNCAP, to Morais GP) and Clementino Fraga Group, Fortaleza, Ceará.

  • Artificial Intelligence (AI) Disclosure

    During the preparation of this manuscript, a large language model (Gemini, Google) was used solely for language editing and stylistic improvements in select paragraphs. No sections involving the generation, analysis, or interpretation of research data were produced by generative AI. All scientific content was created and verified by the authors. Furthermore, no figures or visual data were generated or modified using generative AI or machine learning–based image enhancement tools.

  • Received September 18, 2025.
  • Revision received October 10, 2025.
  • Accepted October 13, 2025.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

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Frequency and Diagnostic Utility of the −13910C>T MCM6 Gene Polymorphism for Lactose Intolerance in a Brazilian Northeast Population
GUILHERME PASSOS DE MORAIS, ANDRÉ PONTES THÉ, BEATRIZ MARIA DIAS NOGUEIRA, DEIVIDE DE SOUSA OLIVEIRA, LEIDIVAN SOUSA DA CUNHA, JEAN BRENO SILVEIRA DA SILVA, PATRÍCIA MARIA PONTES THÉ, ALEXANDRE DE ALMEIDA MONTEIRO, LUIS GONZAGA MOURA XAVIER, MARIA ELISABETE AMARAL DE MORAES, CAROLINE AQUINO MOREIRA-NUNES
In Vivo Jan 2026, 40 (1) 178-190; DOI: 10.21873/invivo.14183
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