Map of the geographic locations of the study populations in the region of West Mexico. Native Amerindians included were Nahuas and Huicholes living in the state of Jalisco and Nayarit, respectively. Mestizos included in this study were from Villa Purificación and Cuquio towns in the state of Jalisco with historical predominant Caucasian ancestry, as well as from the city of Guadalajara in the state of Jalisco and from the city of Tepic in the state of Nayarit.  

Map of the geographic locations of the study populations in the region of West Mexico. Native Amerindians included were Nahuas and Huicholes living in the state of Jalisco and Nayarit, respectively. Mestizos included in this study were from Villa Purificación and Cuquio towns in the state of Jalisco with historical predominant Caucasian ancestry, as well as from the city of Guadalajara in the state of Jalisco and from the city of Tepic in the state of Nayarit.  

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Background/aim: Lactase (LCT) -13910 C>T and -22018 G>A polymorphisms associated with the lactase non-persistence (LNP)/persistence (LP) phenotypes vary globally. LP has been associated with obesity in Europeans. However, it has not been genetically evaluated in Mexico, a country with admixed population, recent introduction of dairy, and a high pr...

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... 28 Habitual food consumption was considered at least three times a week, as previously reported. 29 Eating behaviors (such as eating schedules, the use of electronic devices when eating, and away-from-home food intake) were evaluated based on a validated Mexican questionnaire. 30 ...
Article
Background: The aim of this study was to determine the prevalence of food addiction (FA) in undergraduate students from Northwest Mexico and to examine its association with lifestyle factors, eating behaviors and food consumption.Methods: This cross-sectional study included a total of 326 undergraduate students, both sexes, between 18 and 25 years of age, who were enrolled in a bachelor’s degree program at a public or private university in the city of Tijuana, Baja California, Mexico. FA was assessed using the modified Yale Food Addiction Scale Version 2.0 (mYFAS 2.0). Lifestyle (sleep patterns, physical exercise, alcohol intake, and smoking) and nutritional information (eating behaviors and food frequency consumption) was obtained through a clinical history. A multivariate logistic regression model was fitted to assess the factors associated with FA.Results: The whole prevalence of FA was 12.9%. In general, mild FA was the most frequent (5.2%), followed by severe (4.3%) and moderate (3.4%) categories. In the multivariate model, insomnia conferred a higher risk for FA (OR = 2.08, 95% CI, 1.04–4.17, p = 0.040), while the habitual consumption of fruits showed a protective effect (OR = 0.50, 95% CI, 0.25–0.98, p = 0.046). Overall, the model predicted FA in 12% (R²=0.12, p = 0.011).Conclusion: The prevalence of FA is 12.9% among undergraduate students from Northwest Mexico. Although caution should be exercised, insomnia seems to increase the risk of FA, while the habitual consumption of fruits appears to have a protective role. Additional studies are needed to validate these results.
... Despite breeding these animals, there is no archeological or cultural evidence of dairy consumption by Native American populations until Europeans arrived in the late fifteenth century (Gade, 1999) -cattle were not introduced in the Americas until 1493 (Primo, 1992). Not surprisingly, studies regarding living Native Americans from Brazil (Friedrich et al., 2012a), Chile (Fernández et al., 2016), Ecuador (Paz-Y-Miño et al., 2016), Mexico (Ojeda-Granados et al., 2016), Peru (Figueroa et al., 1971), and the United States (Duncan and Scott, 1972;Casey, 2005) identified lower LP phenotype frequencies in these populations (20% on average), suggesting that most people cannot digest lactose naturally. Countries such as Peru, Mexico, and Chile have a high proportion of Native American ancestry -80, 57.5, and 49.3%, respectively (Ruiz-Linares et al., 2014;Adhikari et al., 2016;Harris et al., 2018) -which could explain the low frequency of the LP phenotype. ...
... Therefore, the phenotypic variation observed is mainly due to the -13910C > T (rs4988235) substitution of European origin. Thus, the admixture events that led to the formation of current Latin American populations contributed to introducing LP-associated alleles in these groups (Friedrich et al., 2012a;Mendoza Torres et al., 2012;Latorre et al., 2014;Fernández et al., 2016;Ojeda-Granados et al., 2016;Paz-Y-Miño et al., 2016;Valencia et al., 2017;Montalva et al., 2019). Consequently, higher frequencies of the LP phenotype are observed in admixed populations from Brazil (Friedrich et al., 2012b), and Mestizos from Chile (Fernández et al., 2016), Colombia (Mendoza Torres et al., 2012), Ecuador (Paz-Y-Miño et al., 2016), and Mexico (Ojeda-Granados et al., 2016. ...
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In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the –13910∗T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase persistence phenotype, the –13910C > T (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products. In the Americas, there is no evidence of the consumption of these products until the arrival of Europeans. However, several American countries’ dietary guidelines recommend consuming dairy for adequate human nutrition and health promotion. Considering the extensive use of dairy and the complex ancestry of Pan-American admixed populations, we studied the distribution of –13910C > T lactase persistence genotypes and its flanking haplotypes of European origin in 7,428 individuals from several Pan-American admixed populations. We found that the –13910∗T allele frequency in Pan-American admixed populations is directly correlated with allele frequency of the European sources. Moreover, we did not observe any overrepresentation of European haplotypes in the –13910C > T flanking region, suggesting no selective pressure after admixture in the Americas. Finally, considering the dominant effect of the –13910∗T allele, our results indicate that Pan-American admixed populations are likely to have higher frequency of lactose intolerance, suggesting that general dietary guidelines deserve further evaluation across the continent.
... Furthermore, a preceding analysis of DRAG polymorphisms in Mexican populations showed a high prevalence of adaptive alleles (methylenetetrahydrofolate reductase-MTHFR 677T, ATP-binding cassette transporter A1-ABCA1 230C, apolipoprotein E -APOE ε4, and a salivary amylase 1-AMY1 diploid copy number ≥ 6) mainly in NA groups followed by admixed populations (Mestizo) with an intermediate NA ancestry, while a very low frequency of the European lactase-persistence LCT-13910T adaptive allele was observed [9]. These findings suggest that carriers of the adaptive alleles might require nutritional needs concordant with the pre-Hispanic diet and practices to prevent current disease-related risks [10][11][12][13][14][15][16]. In line with this hypothesis is the fact that polymorphism-disease associations are not replicated when studying populations that follow their traditional diet and lifestyle [17,18]. ...
... The traditional Mexican diet improved insulin sensitivity (HOMA-IR), lowered serum concentrations of insulin-like growth factor-binding protein-3 (IGFBP-3), and tended to reduce concentrations of insulin-like growth factor-1 (IGF-1) under conditions of weight stability, while no difference in inflammatory response was revealed. However, that diet incorporated full-fat milk, which was one of the foods discarded in our study due to the high prevalence of the lactase non-persistence genotype in Mexico [15]. ...
... In particular, the regionalized GENOMEX diet was designed considering some DRAG polymorphisms [9] that in modern dietary and lifestyle environments have been associated with increased risk of unhealthy conditions [10][11][12][13][14][15][16]. Accordingly, we assumed that carriers of the adaptive alleles might require nutritional needs related to the main features of the pre-Hispanic diet (i.e., milk-free, scarce in animal meat, low in saturated fat and cholesterol, with low glycemic index and rich in antioxidants, fiber, and micronutrients such as folates due to the abundance of starchy foods, legumes, vegetables, and fruits). ...
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Obesity-related chronic diseases (CD) are highly prevalent in Mexicans who show moderate to high frequencies of diet-related adaptive gene (DRAG) polymorphisms and recent shifts in traditional dietary habits and lifestyles. This study first evaluated the effects of a regionalized genome-based Mexican (GENOMEX) diet on anthropometric and biochemical parameters and, subsequently their relationship with the genetic profile of DRAG polymorphisms in subjects with metabolic risk factors for obesity-related CD. Thirty-seven eligible subjects underwent a 24-week dietary intervention with a GENOMEX diet. The DRAG polymorphisms were determined by an allelic discrimination real-time assay to evaluate their association with the clinical response to diet. The GENOMEX diet significantly improved anthropometric parameters such as total weight, body mass index, waist circumference, and body fat percentage, with an average weight loss of 6.6% (5.3 ± 5.3 kg). The frequency of subjects with insulin resistance, hypertriglyceridemia and elevated VLDL-c (48.5% vs. 24.2%, p = 0.041; 45.5% vs. 12.1%, p = 0.003; and 39.4% vs. 15.2%, p = 0.027, baseline vs. 24-weeks, respectively) was reduced. A more significant favorable effect in HOMA-IR and insulin was observed in MTHFR 677T adaptive allele carriers, but no other DRAG polymorphism was associated with clinical changes. The GENOMEX diet improved the metabolic risk factors for obesity-related CD. The recommendation and habitual consumption of a traditional Mexican diet based on knowledge of the population´s genetic and cultural history may be effective in preventing current obesity-related CD.
... The number of participants of African descent, who may express other variants that confer lactase persistence, was particularly low (n = 13). Populations of Native American ancestry, who were excluded from dietary analysis in this study due to low numbers ("Other" ethnicity), had high proportions of the LNP genotype (GG, 68.2%) and low dairy consumption in another study [50]. Participants of Middle Eastern descent were also included in "Other" ethnicity group; a study of seven Iranian populations found LP in 0 to 29.9% of the groups with significant associations between rs4988235, which is another LP-related SNP (ID: rs182549), and the LP phenotype [51]. ...
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Lactase persistence (LP) is a trait in which lactose can be digested throughout adulthood, while lactase non-persistence (LNP) can cause lactose intolerance and influence dairy consumption. One single nucleotide polymorphism (SNP ID: rs4988235) is often used as a predictor for dairy intake, since it is responsible for LP in people in European descent, and can occur in other ethnic groups. The objective of this study was to determine whether rs4988235 genotypes and ethnicity influence reported dairy consumption in the United States (U.S.). A food frequency questionnaire (FFQ) and multiple Automated Self-Administered 24-h recalls (ASA24®) were used to measure habitual and recent intake, respectively, of total dairy, cheese, cow’s milk, plant-based alternative milk, and yogurt in a multi-ethnic U.S. cohort genotyped for rs4988235. Within Caucasian subjects, LP individuals reported consuming more recent total dairy and habitual total cow’s milk intake. For subjects of all ethnicities, LP individuals consumed more cheese (FFQ p = 0.043, ASA24 p = 0.012) and recent total dairy (ASA24 p = 0.005). For both dietary assessments, Caucasians consumed more cheese than all non-Caucasians (FFQ p = 0.036, ASA24 p = 0.002) independent of genotype, as well as more recent intake of yogurt (ASA24 p = 0.042). LP subjects consumed more total cow’s milk than LNP, but only when accounting for whether subjects were Caucasian or not (FFQ p = 0.015). Fluid milk and alternative plant-based milk consumption were not associated with genotypes or ethnicity. Our results show that both LP genotype and ethnicity influence the intake of some dairy products in a multi-ethnic U.S. cohort, but the ability of rs4988235 genotypes to predict intake may depend on ethnic background, the specific dairy product, and whether intake is reported on a habitual or recent basis. Therefore, ethnicity and the dietary assessment method should also be considered when determining the suitability of rs4988235 as a proxy for dairy intake.
... Lactase deficiency is a common disorder, affecting 5-15% of Caucasians (11) and 44-100% of Hispanics (12,13). Lactase deficiency occurs when the small intestine fails to produce lactase. ...
Article
Background: The risk of neural tube defect (NTD)-affected pregnancies is reduced with adequate folic acid intake during early pregnancy. However, NTDs have been observed among offspring of women with adequate folic acid intake. Some of these women are possibly not absorbing enough folic acid. Because lactase deficiency can lead to poor nutrient absorption, we hypothesized that lactase-deficient women will be at increased risk of having offspring with NTDs. Objective: We examined the association between maternal rs4988235 (a lactase deficiency genetic marker) and NTDs in offspring. Methods: We conducted a case-control study using data from the National Birth Defects Prevention Study, United States, 1997-2009, restricting to non-Hispanic white (NHW) and Hispanic women. Cases were women with an offspring with an NTD (n = 378 NHW, 207 Hispanic), and controls were women with an offspring without a birth defect (n = 461 NHW, 165 Hispanic). Analyses were conducted separately by race/ethnicity, using logistic regression. Women with the CC genotype were categorized as being lactase deficient. To assess potential effect modification, analyses were stratified by lactose intake, folic acid supplementation, dietary folate, and diet quality. Results: Among NHW women, the odds of being lactase deficient were greater among cases compared with controls (OR: 1.37; 95% CI: 1.02, 1.82). Among Hispanic women, the odds of being lactase deficient were significantly lower among cases compared with controls (OR: 0.50, 95% CI: 0.33, 0.77). The association differed when stratified by lactose intake in NHW women (higher odds among women who consumed ≥12 g lactose/1000 kcal) and by dietary folate in Hispanic women (opposite direction of associations). The association did not differ when stratified by folic acid supplementation or diet quality. Conclusions: Our findings suggest that maternal lactase deficiency is associated with NTDs in offspring. However, we observed opposite directions of effect by race/ethnicity that could not be definitively explained.
... In a cross-sectional and analytical study, 215 unrelated West Mexican adults of both genders were enrolled, which have been characterized and genotyped for other nutrient-sensing polymorphisms [36][37][38]. Data collection and clinical assessments were conducted at the Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara 'Fray Antonio Alcalde' in Guadalajara, Jalisco, Mexico from January 2012 to December 2015. Exclusion criteria included a history of cardiovascular, liver, kidney or pancreas disease; women who were pregnant or breastfeeding; active smokers; and subjects who reported consuming a special diet restricted in calories, fat, protein or carbohydrates in the last six months. ...
... Subjects were asked to provide information concerning how frequent they had consumed each food item during the previous six months according to the following frequency categories: "daily", "at least 3 times per week", "1-2 times per week", "once every 15 days" "one a month" and "never". For purposes of this study, habitual consumption of sugar-rich foods was based on "daily" or "at least 3 times per week" categories, whereas the rest of food frequency categories were cataloged as a non-habitual consumption [38]. Frequencies of habitual consumption of sugar-rich foods were then used to evaluate the influence of the C957T DRD2 polymorphism on this behavior, excluding those with a non-habitual consumption. ...
... Similar low frequencies have been reported in Europeans (12.5%), whereas the highest frequencies of this genotype have been found in Asians (88%) and Africans (93%) [44]. According to ancestral estimations of the genetic composition of Mexicans living in different regions throughout the country, our results are consistent with the European ancestry gradient documented in West Mexico [38,45]. However, further research is required to establish the frequencies of C957T DRD2 variants in other regions of Mexico, particularly in populations exposed to different environments. ...
Article
Genetic variations in the dopamine receptor D2 (DRD2) may alter dopamine signaling and modify the rewarding effects of food. This study aimed to analyze the association of the C957T DRD2 polymorphism with sugar consumption in West Mexican subjects. In a cross-sectional and analytical study, a total of 215 Mexican subjects were enrolled. DRD2 genotyping was performed by an allelic discrimination assay. Habitual dietary intake and the biochemical profile were evaluated. Genotype frequencies of the C957T DRD2 polymorphism were CC (12.1%), CT (40.9%) and TT (47.0%). Carriers of the CC genotype had a higher intake of sugar (g/day) than heterozygotes (67.4 g vs. 41.3 g, p = 0.001) and TT homozygotes (67.4 g vs. 45.2 g, p = 0.004). Also, the habitual consumption of soda (daily or at least 3 times per week) was more frequent among CC genotype carriers compared with heterozygotes (81% vs. 51%, p = 7.5 × 10-6) and TT homozygotes (81% vs. 57%, p = 2.4 × 10-4). Furthermore, the CC genotype was associated with elevated serum triglyceride levels (>150 mg/dL) than the CT genotype (OR = 2.80, 95% CI 1.08-7.24, p = 0.034). In conclusion, our results suggest a genetic background associated with sugar consumption among West Mexicans, which may contribute to increases in serum triglyceride levels.
... The Mestizo population comprise a variable proportion of AM, European (EUR) and African ancestry depending on the geographic region [21]. For instance, Central West (CW) Mexico harbors a heterogeneous population, with ethnic groups having a high amount of AM ancestry and Mestizos having an intermediate AM ancestry or predominantly EUR ancestry (Mestizos-EUR) [22][23][24]. This recent genetic admixture explains the presence in Mexicans of DRAG polymorphisms identified in other populations worldwide. ...
... This recent genetic admixture explains the presence in Mexicans of DRAG polymorphisms identified in other populations worldwide. Such is the case, for example, of the LCT C-13910T variant related to lactase persistence in EUR, which has been found in Mexican subpopulations with high EUR ancestry but is absent in AM subpopulations [24]. ...
... To assess the frequency of DRAG polymorphisms in the CW Mexico region, genotyping of rs1801133, rs9282541, rs429358, and rs7412 and determination of AMY1 copy number were performed in different subpopulations with DNA samples of unrelated individuals obtained in previous studies by our research group [23,24]. The subpopulations were the ethnic groups Huichol (n = 99) and Nahuas (n = 84); Mestizos from Tepic in Nayarit State (n = 184) and Guadalajara in Jalisco State (n = 768); and Mestizos-EUR from the towns Cuquio (n = 131), Villa Purificación (n = 32) and San Miguel el Alto (n = 33) in Jalisco. ...
Article
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Diet-related adaptive gene (DRAG) polymorphisms identified in specific populations are associated with chronic disorders in carriers of the adaptive alleles due to changes in dietary and lifestyle patterns in recent times. Mexico’s population is comprised of Amerindians (AM) and Mestizos who have variable AM, European (EUR) and African genetic ancestry and an increased risk of nutrition-related chronic diseases. Nutritional advice based on the Mexican genome and the traditional food culture is needed to develop preventive and therapeutic strategies. Therefore, we aimed to provide a prevalence profile of several DRAG polymorphisms in the Mexican population, including Central West (CW) Mexico subpopulations. Geographic heat maps were built using ArcGIS10 (Esri, Redlands, CA, USA) software, based on the published data of the MTHFR C677T (rs1801133), ABCA1 Arg230Cys (rs9282541), APOE T388C (rs429358)/C526T (rs7412), LCT C-13910T (rs4988235) polymorphisms and AMY1 copy number variation (CNV). Also, new data obtained by allelic discrimination-real-time polymerase chain reaction (RT-PCR) assays for the MTHFR, ABCA1, and APOE polymorphisms as well as the AMY1 CNV in the CW Mexico subpopulations with different proportions of AM and EUR ancestry were included. In the CW region, the highest frequency of the MTHFR 677T, ABCA1 230C and APOE ε4 adaptive alleles was observed in the AM groups, followed by Mestizos with intermediate AM ancestry. The LCT-13910T allele frequency was highest in Mestizos-EUR but extremely low in AM, while the AMY1 diploid copy number was 6.82 ± 3.3 copies. Overall, the heat maps showed a heterogeneous distribution of the DRAG polymorphisms, in which the AM groups revealed the highest frequencies of the adaptive alleles followed by Mestizos. Given these genetic differences, genome-based nutritional advice should be tailored in a regionalized and individualized manner according to the available foods and Mexican traditional food culture that may lead to a healthier dietary pattern.
... For example, most populations in Latin America countries, such as Mexico are an admixture of Amerindian, Caucasian and African lineages with a rich and traditional food culture. Recent studies in the Mexican population have revealed a higher prevalence of risk alleles of sweet (TAS1R2) [107] , fat (CD36) [108,109] and bitter (TAS2R38) [110] taste receptors, lipidtransporting proteins (APO e2 and e4, FABP2) [111] , lactose intolerance (LCT13910 C>T) [112] and neurotransmitter transporters (DRD2 Taq1) [113] . These alleles have been associated with metabolic abnormalities, obesity and alcohol abuse disorders, aggravated by the consumption of a hepatopathogenic and obesogenic diet [114] . ...
Article
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Most medical specialties including the field of gastroenterology are mainly aimed at treating diseases rather than preventing them. Genomic medicine studies the health/disease process based on the interaction of the human genes with the environment. The gastrointestinal (GI) system is an ideal model to analyze the interaction between our genes, emotions and the gut microbiota. Based on the current knowledge, this mini-review aims to provide an integrated synopsis of this interaction to achieve a better understanding of the GI disorders related to bad eating habits and stress-related disease. Since human beings are the result of an evolutionary process, many biological processes such as instincts, emotions and behavior are interconnected to guarantee survival. Nourishment is a physiological need triggered by the instinct of survival to satisfy the body’s energy demands. The brain-gut axis comprises a tightly connected neural-neuroendocrine circuitry between the hunger-satiety center, the dopaminergic reward system involved in the pleasure of eating and the gut microbiota that regulates which food we eat and emotions. However, genetic variations and the consumption of high-sugar and high-fat diets have overridden this energy/pleasure neurocircuitry to the point of addiction of several foodstuffs. Consequently, a gut dysbiosis generates inflammation and a negative emotional state may lead to chronic diseases. Balancing this altered processes to regain health may involve personalized-medicine and genome-based strategies. Thus, an integrated approach based on the understanding of the gene-emotions-gut microbiota interaction is the next frontier that awaits the gastroenterologist to prevent and treat GI disorders associated with obesity and negative emotions.
... A single nucleotide polymorphism (rs4988235) located at position -13910 upstream of the LCT gene has been shown to regulate lactase expression (11) and has been associated with LI in >70 ethnically diverse populations (12). The ancestral genotype is associated with symptoms of LI (11), lower milk consumption (13)(14)(15), and diminished lactase activity in European-derived populations (11,12,16). The ratio of sucrase to lactase (S:L) enzyme activity in the CC genotype is consistent with the cutoff for LI (12). ...
Article
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Background: The LCT-13910C>T gene variant is associated with lactose intolerance (LI) in different ethnic groups. Individuals with LI often limit or avoid dairy consumption, a major dietary source of vitamin D in North America, which may lead to inadequate vitamin D intake. Objective: The objective was to determine the prevalence of genotypes predictive of LI in different ethnic groups living in Canada and to determine whether the LCT genotype is associated with plasma 25(OH)D concentrations. Methods: Blood samples were drawn from a total of 1495 men and women aged 20–29 y from the Toronto Nutrigenomics and Health Study for genotyping and plasma 25(OH)D analysis. Intakes of dairy were assessed by using a 196-item food frequency questionnaire. The prevalence of LCT-13910C>T genotypes was compared by using χ² analysis. Using a Mendelian randomization approach, we examined the association between LCT genotypes and 25(OH)D concentrations. Results: Approximately 32% of Caucasians, 99% of East Asians, 74% of South Asians, and 59% of those with other or mixed ethnicities had the CC genotype associated with LI. Compared with those with the TT genotype, those with the CC genotype had a lower mean ± SE total dairy intake (2.15 ± 0.09 compared with 2.67 ± 0.12 servings/d, P = 0.003), a lower skim-milk intake (0.20 ± 0.03 compared with 0.46 ± 0.06 servings/d, P = 0.0004), and a lower plasma 25(OH)D concentration (63 ± 1.9 compared with 75.8 ± 2.4 nmol/L, P < 0.0001). The CT and CC genotypes were associated with a 50% and a 2-fold increased risk, respectively, of a suboptimal plasma 25(OH)D concentration (<75 nmol/L). Conclusions: In Caucasians, the CC genotype that predicts LI is associated with a lower plasma 25(OH)D concentration, which is attributable at least in part to a lower intake of dairy, particularly skim milk. Increased risk of suboptimal concentrations of vitamin D was also observed among those with the CT genotype, suggesting an intermediate effect of the heterozygous genotype.
... In West Mexico, the Mestizos from the city of Guadalajara have more Caucasian ancestry than Amerindian, whereas an inverted proportion of ancestries is seen in the Mestizos of Tepic (Ojeda-Granados et al., 2016), alongside with the Huicholes and Nahuas who are part of the 15 million Amerindians nationwide (CDI). In this study, the pattern of genetic clustering shown in the MDS plot was in agreement with these documented backgrounds, displaying the influence of the Amerindian ancestry of the DRD2/ANKK1 A1 alleles that was higher in the Natives and the HD of the Mestizos of Tepic (Fig. 1). ...
Article
Background: Mexico has an ancient tradition of alcohol drinking influenced by genetic and sociocultural factors. This study aimed to determine the distribution of the DRD2/ANKK1 TaqIA polymorphism in Mexican populations and to analyze its association with heavy drinking. Methods: In a cross-sectional and analytical study, 680 unrelated subjects including two Native Amerindians groups (87 Nahuas and 139 Huicholes), and two Mestizos groups (158 subjects from Tepic, Nayarit and 296 subjects from Guadalajara, Jalisco) were enrolled. DRD2/ANKK1 genotyping was performed by PCR-RFLP and allelic discrimination assays. Genetic analyses were conducted by Arlequin and Structure software. Heavy drinking was defined as ≥300g alcohol/week. The association of the DRD2/ANKK1 TaqIA polymorphism with heavy drinking was estimated. Results: Heavy drinking was prevalent in 64.7% of the study population. The DRD2/ANKK1 A1 allele prevailed in 67% and 65% of Nahuas and Huicholes, respectively and 51% and 47.3% in Mestizos from Tepic and Guadalajara, respectively. Heavy drinking was associated with the A1A1 genotype in the Mestizos of Guadalajara (A1A1 vs. A1A2 OR=4.79, 95%CI 1.81-12.68, p=0.0006; A1A1 vs. A1A2+A2A2, OR=4.09, 95%CI 1.56-10.68, p=0.0021) and in the Mestizos from Tepic (A1A1 vs. A1A2, OR=5.92, 95%CI 2.12-16.49, p=0.0002); A2A2, OR=14.56, 95%CI 3.57-59.24, p=0.00004); A1A2+A2A2, OR=6.68, 95%CI 2.42-18.42, p=0.00005). In Native Amerindians, a lack of association was found. Conclusions: High frequencies of the DRD2/ANKK1 A1 allele were present in Mexican populations. Native Amerindians exhibited the highest frequencies of the A1 allele documented worldwide to date. The A1A1 genotype was associated with heavy drinking in Mestizos.