A combined linkage and association strategy identifies a variant near the GSTP1 gene associated with BMI in the Mexican population

Abstract

Obesity is a major public health concern in Mexico and worldwide. Although the estimated heritability is high, common variants identified by genome-wide association studies explain only a small proportion of this heritability. A combination of linkage and association strategies could be a more robust and powerful approach to identify other obesity-susceptibility variants. We thus sought to identify novel genetic variants associated with obesity-related traits in the Mexican population by combining these methods. We performed a genome-wide linkage scan for body mass index (BMI) and other obesity-related phenotypes in 16 Mexican families using the Sequential Oligogenic Linkage Analysis Routines Program. Associated single-nucleotide polymorphisms (SNPs) were tested for associations in an independent cohort. Two suggestive BMI-linkage peaks (logarithm of odds ⩾1.5) were observed at chromosomal regions 11q13 and 13q22. Only rs614080 in the 11q13 region was significantly associated with BMI and related traits in these families. This association was also significant in an independent cohort of Mexican adults. Moreover, this variant was significantly associated with GSTP1 gene expression levels in adipose tissue. In conclusion, the rs614080 SNP near the GSTP1 gene was significantly associated with BMI and GSTP1 expression levels in the Mexican population.

Influence of GSTT1 and GSTP1 polymorphisms on type 2 diabetes mellitus and diabetic retinopathy risk in the Chinese population: a case control study

“…But the molecular mechanisms and physiological functions of GSTs in this pathway is still unknown. It has been reported that the rs614080 SNP near GSTP1 gene was associated with higher BMI and GSTP1 expression levels in subcutaneous adipose tissue in the Mexican population, which indicating the role of GSTP1 in human obesity (41). Moreover, the de ciency of GSTP could induce glucose intolerance via JNK (its activation can trigger insulin resistance)-dependent enhancement of hepatic gluconeogenesis (42).…”

Bebidas azucaradas: la batalla contra el sobrepeso y la obesidad en México

“…Por ejemplo, pueden ser causadas por la carga genética, los malos hábitos de alimentación y/o la vida sedentaria. Aunque diversas investigaciones, como las realizadas en el Instituto Nacional de Medicina Genómica (inmegen) por el grupo de Canizales Quinteros, sugieren que la carga genética del mexicano promueve el desarrollo de la obesidad (León-Mimila et al, 2013;Villamil-Ramírez et al, 2017). Considerando que esta pandemia es un producto de casi cuatro décadas, limitarse a la carga genética como la única explicación, no parece factible.…”