Association of the T130I Variant of the HNF4A Gene with Metabolic Syndrome and Its Components in Mexican Children.

Background: Metabolic syndrome (MetS), a cluster of risk factors, leads to cardiovascular disease (CVD) and type 2 diabetes (T2D). The second leading cause of mortality in Mexico is T2D. Genetic factors participate in the pathogenesis of MetS. The HNFA gene encodes a transcription factor that plays a crucial role in energy homeostasis by regulating the metabolism of glucose and lipids. This study aimed to investigate the association of the T130I variant of the HNF4A gene in Mexican children with MetS and its constituent components. Methods: The study was performed in 477 children from elementary schools. MetS was classified according to the de Ferranti definition. Biochemical parameters were measured and genotyping was performed. Logistic regression under a dominant genetic model was used to analyze the association of the T130I variant of the HNF4A gene with MetS and with its components separately. Results: The prevalence of MetS was 25.4%, and 18.9% in children who presented insulin resistance. Interestingly, this is the first time that a significant association between the T130I variant of the HNF4A gene and MetS has been reported [odds ratios (OR) = 2.31; 95% confidence interval (CI) 1.10-4.83; P = 0.026]. Moreover, carriers of the risk allele show higher abdominal obesity (OR = 1.20; 95% CI 1.09-4.50; P = 0.029). These findings highlight the active role of genetic variants in the pathogenesis of MetS in Mexican children. Conclusions: The high prevalence of children with MetS and insulin resistance places this population at an elevated risk of early CVD and T2D. The Clinical Trial Registration Number is HJM2315/14C.

Genetic variability of CYP2C9*2 and CYP2C9*3 in seven indigenous groups from Mexico.

AIM: CYP2C9 is one of the major drug metabolizing enzymes, however, little is known about polymorphisms in CYP2C9 gene and pharmacological implications in Mexican indigenous populations. Thus, frequencies of CYP2C9*2 and CYP2C9*3 alleles were evaluated in indigenous groups located in northwest (Cora), center (Mazahua and Teenek), south (Chatino and Mixteco) and southeast (Chontal and Maya) regions Mexico. MATERIALS & METHODS: Allelic discrimination was performed by real-time PCR. RESULTS: CYP2C9*2 allele was found only in Chontal and Maya groups, despite the low contribution of Caucasian component in these populations. CYP2C9*3 allele was present in all populations except in Mazahua, showing a wide genetic variability in the studied populations. Interestingly, we found significant differences between indigenous groups in CYP2C9*3 allele, even in groups located at the same region and belonging to the same linguistic family. CONCLUSION: These results contribute to laying the pharmacogenetic bases in Mexico, in addition to improving treatment, taking into account the genetic interethnic differences.