The ATP-binding cassette transporter A1 (ABCA1) R230C variant is associated with low HDL cholesterol levels, obesity, and the metabolic syndrome in Mexican-Mestizos. Because a pivotal role for ABCA1 ...in pancreatic beta-cell function was recently observed in the mouse model, we assessed the association of this variant with type 2 diabetes in this population.
The initial group included 446 unrelated Mexican individuals: 244 with type 2 diabetes aged 20-69 years (121 with onset </=45 years), and 202 nondiabetic control subjects aged >50 years. An independent study group included 242 type 2 diabetic case subjects and 225 control subjects with similar characteristics.
R230C/C230C genotypes were significantly more frequent in type 2 diabetic individuals (24.6%) than in control subjects (11.4%) in the initial study group (OR 2.501; P = 0.001). After stratifying by age at diagnosis, the association was significant only in the early-onset group (age at diagnosis </=45 years) (OR 3.776, P = 3.3 x 10(-6)). Both associations remained significant after adjusting for admixture (P = 0.0008 and P = 8.1 x 10(-6), respectively). Similar trends were observed in the independent study group, and the combined analysis of both populations showed a highly significant association of the R230C variant with type 2 diabetes, particularly with that of early onset (P = 7.6 x 10(-6) and 9.4 x 10(-8), respectively).
The R230C ABCA1 variant is associated with type 2 diabetes, particularly of early onset, in the Mexican-Mestizo population.
Although ATP-binding cassette transporter A1 (ABCA1) is well known for its role in cholesterol efflux and HDL formation, it is expressed in various tissues, where it may have different functions. ...Because hypoalphalipoproteinemia is highly prevalent in Mexico, we screened the ABCA1 coding sequence in Mexican individuals with low and high HDL cholesterol levels to seek functional variants. A highly frequent nonsynonymous variant (R230C) was identified in low-HDL cholesterol but not in high-HDL cholesterol individuals (P = 0.00006). We thus assessed its frequency in the Mexican-Mestizo general population, seeking possible associations with several metabolic traits. R230C was screened in 429 Mexican Mestizos using Taqman assays, and it was found in 20.1% of these individuals. The variant was significantly associated not only with decreased HDL cholesterol and apolipoprotein A-I levels but also with obesity (odds ratio 2.527, P = 0.005), the metabolic syndrome (1.893, P = 0.0007), and type 2 diabetes (4.527, P = 0.003). All of these associations remained significant after adjusting for admixture (P = 0.011, P = 0.001, and P = 0.006, respectively). This is the first study reporting the association of an ABCA1 variant with obesity and obesity-related comorbidities as being epidemiologically relevant in the Mexican population.
Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disease characterized by progressive cerebellar ataxia and macular degeneration causing progressive blindness. It accounts for 1 to ...11.6 % of spinocerebellar ataxias (SCAs) cases worldwide and for 7.4 % of SCA7 cases in Mexico. We identified a cluster of SCA7 families who resided in a circumscribed area of Veracruz and investigated whether the high incidence of the disease in this region was due to a founder effect. A total of 181 individuals from 20 families were studied. Four microsatellite markers and one SNP flanking the
ATNX7
gene were genotyped and the ancestral origin and local ancestry analysis of the SCA7 mutation were evaluated. Ninety individuals from 19 families had the SCA7 mutation; all were found to share a common haplotype, suggesting that the mutation in these families originated from a common ancestor. Ancestral origin and local ancestry analysis of SCA7 showed that the chromosomal segment containing the mutation was of European origin. We here present evidence strongly suggesting that the high frequency of SCA7 in Veracruz is due to a founder effect and that the mutation is most likely of European origin with greatest resemblance to the Finnish population.
Common polymorphisms in the fat mass and obesity‐associated gene (FTO) have shown strong association with obesity in several populations. In the present study, we explored the association of FTO gene ...polymorphisms with obesity and other biochemical parameters in the Mexican population. We also assessed FTO gene expression levels in adipose tissue of obese and nonobese individuals. The study comprised 788 unrelated Mexican‐Mestizo individuals and 31 subcutaneous fat tissue biopsies from lean and obese women. FTO single‐nucleotide polymorphisms (SNPs) rs9939609, rs1421085, and rs17817449 were associated with obesity, particularly with class III obesity, under both additive and dominant models (P = 0.0000004 and 0.000008, respectively). These associations remained significant after adjusting for admixture (P = 0.000003 and 0.00009, respectively). Moreover, risk alleles showed a nominal association with lower insulin levels and homeostasis model assessment of B‐cell function (HOMA‐B), and with higher homeostasis model assessment of insulin sensitivity (HOMA‐S) only in nonobese individuals (P dom = 0.031, 0.023, and 0.049, respectively). FTO mRNA levels were significantly higher in subcutaneous fat tissue of class III obese individuals than in lean individuals (P = 0.043). Risk alleles were significantly associated with higher FTO expression in the class III obesity group (P = 0.047). In conclusion, FTO is a major risk factor for obesity (particularly class III) in the Mexican‐Mestizo population, and is upregulated in subcutaneous fat tissue of obese individuals.
Culture and genetics rely on two distinct but not isolated transmission systems. Cultural processes may change the human selective environment and thereby affect which individuals survive and ...reproduce. Here, we evaluated whether the modes of subsistence in Native American populations and the frequencies of the ABCA1*Arg230Cys polymorphism were correlated. Further, we examined whether the evolutionary consequences of the agriculturally constructed niche in Mesoamerica could be considered as a gene-culture coevolution model. For this purpose, we genotyped 229 individuals affiliated with 19 Native American populations and added data for 41 other Native American groups (n = 1905) to the analysis. In combination with the SNP cluster of a neutral region, this dataset was then used to unravel the scenario involved in 230Cys evolutionary history. The estimated age of 230Cys is compatible with its origin occurring in the American continent. The correlation of its frequencies with the archeological data on Zea pollen in Mesoamerica/Central America, the neutral coalescent simulations, and the F(ST)-based natural selection analysis suggest that maize domestication was the driving force in the increase in the frequencies of 230Cys in this region. These results may represent the first example of a gene-culture coevolution involving an autochthonous American allele.
Risk of hyperuricemia is modified by genetic and environmental factors. Our aim was to identify factors associated with serum uric acid levels and hyperuricemia in Mexicans. A pilot Genome-wide ...association study GWAS was performed in a subgroup of participants (
= 411) from the Health Workers Cohort Study (HWCS). Single nucleotide polymorphisms (SNPs) associated with serum uric acid levels were validated in all the HWCS participants (
= 1939) and replicated in independent children (
= 1080) and adult (
= 1073) case-control studies. The meta-analysis of the whole HWCS and replication samples identified three
SNPs:
(
= 2.3 × 10
),
(
= 8.2 × 10
) and
(
= 1.1 × 10
); and an
missense SNP,
(
= 1.0 × 10
). Among the non-genetic factors identified, the visceral adiposity index, smoking, the metabolic syndrome and its components (waist circumference, blood pressure, glucose and hyperlipidemia) were associated with increased serum uric acid levels and hyperuricemia (
< 0.05). Among the female HWCS participants, the odds ratio for hyperuricemia was 1.24 (95% CI, 1.01-1.53) per unit increase in soft drink consumption. As reported in other studies, our findings indicate that diet, adiposity and genetic variation contribute to the elevated prevalence of hyperuricemia in Mexico.
Please see the corrected table here: thumbnail Download: * PPT PowerPoint slide * PNG larger image * TIFF original image ^ Figures Citation: Hünemeier T, Amorim CEG, Azevedo S, Contini V, ...Acuña-Alonzo V, Rothhammer F, et al. (2012) Correction: Evolutionary Responses to a Constructed Niche: Ancient Mesoamericans as a Model of Gene-Culture Coevolution.
Several studies suggest an important role of Interleukin-27 in the development of atherosclerosis. The aim of this study was to establish whether the
gene polymorphisms are associated with premature ...coronary artery disease and/or other cardiovascular risk factors. Four
gene polymorphisms were selected and genotyped in 1162 premature coronary artery disease cases and 1107 controls. rs26528
and rs40837
alleles were significantly associated with a lower risk of premature coronary artery disease under different inheritance models (P
= 0.046; P
= 0.002; P
= 0.007 for rs26528T; P
= 0.008 and P
= 0.031 for rs40837). The rs40837
allele was also associated with a lower risk of insulin resistance, in cases (P
= 0.037) and controls (P
= 0.008; P
= 0.047; P
= 0.014; P
= 0.006), while the rs26528
allele was associated with a lower risk of insulin resistance only in the control group (P
= 0.016; P
= 0.021). Interleukin-27 plasma levels were measured in 450 controls and 450 cases, and were significantly higher in cases compared to controls (P = 0.004). However, Interleukin-27 plasma levels were not associated with
polymorphisms. Luciferase assays showed that co-transfection of the rs40837
allele and miR-379-5p significantly decreased luciferase gene expression. Our study shows for the first time, that IL
gene polymorphisms are associated with premature coronary artery disease and with some metabolic parameters. The rs40837
allele in presence of miR-379-5p significantly decreased luciferase gene expression.
Non-alcoholic fatty liver disease (NAFLD) and elevated alanine transaminase (ALT) levels are common in obese Hispanic adults and children. Recently, a PNPLA3 gene variant (I148M) was strongly ...associated with NAFLD and higher ALT levels in obese adults, including Hispanics. The aims of this study were to estimate the frequency of elevated ALT levels, and to address the influence of obesity and PNPLA3/I148M on ALT levels in a general population sample of Mexican school-aged children.
A total of 1037 non-related Mexican children aged 6 to 12years were genotyped for the I148M variant. Anthropometric, clinical and metabolic parameters were collected from all participants.
Elevated ALT levels (>35U/L) were more frequent in obese (26.9%) and overweight (9.3%) than in normal weight children (2.2%). The M148M genotype was significantly associated with elevated ALT levels in this population (OR=3.7, 95% CI 2.3–5.9; P=3.7×10−8), and children carrying the M148M genotype showed significantly lower HDL cholesterol levels and BMI z-core (P=0.036 and 0.015, respectively). On stratifying by BMI percentile, this genotype conferred a much greater risk of elevated ALT levels in normal weight (OR=19.9, 95% CI 2.5–157.7; P=0.005) than overweight and obese children (OR=3.4, 95% CI 1.3–8.9; P=0.014 and OR=3.1, 95% CI 1.7–5.5; P=1.4 x10−4, respectively).
The I148M PNPLA3 variant is strongly associated with elevated ALT levels in normal weight and overweight/obese Mexican children. Thus, the M148M genotype may be considered as an important risk factor for liver damage in this population.
•We report the effect of obesity and PNPLA3/I148M on ALT levels in Mexican children.•High ALT levels are more common in obese/overweight than in normal weight children.•PNPLA3/I148M is associated with high ALT levels in obese, overweight and normal weight children.•Carriers of the M148M genotype had lower HDL cholesterol levels and BMI z-core.
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