Replication of obesity and diabetes-related SNP associations in individuals from Yucatán, México

Abstract

The prevalence of type 2 diabetes (T2D) is rising rapidly and in Mexicans is ~19%. T2D is affected by both environmental and genetic factors. Although specific genes have been implicated in T2D risk few of these findings are confirmed in studies of Mexican subjects. Our aim was to replicate associations of 39 single nucleotide polymorphisms (SNPs) from 10 genes with T2D-related phenotypes in a community-based Mexican cohort. Unrelated individuals (n = 259) living in southeastern Mexico were enrolled in the study based at the University of Yucatan School of Medicine in Merida. Phenotypes measured included anthropometric measurements, circulating levels of adipose tissue endocrine factors (leptin, adiponectin, pro-inflammatory cytokines), and insulin, glucose, and blood pressure. Association analyses were conducted by measured genotype analysis implemented in SOLAR, adapted for unrelated individuals. SNP Minor allele frequencies ranged from 2.2 to 48.6%. Nominal associations were found for CNR1, SLC30A8, GCK, and PCSK1 SNPs with systolic blood pressure, insulin and glucose, and for CNR1, SLC30A8, KCNJ11, and PCSK1 SNPs with adiponectin and leptin (p < 0.05). P-values greater than 0.0014 were considered significant. Association of SNPs rs10485170 of CNR1 and rs5215 of KCNJ11 with adiponectin and leptin, respectively, reached near significance (p = 0.002). Significant association (p = 0.001) was observed between plasma leptin and rs5219 of KCNJ11.

Genetic variants in KCNJ11, TCF7L2 and HNF4A are associated with type 2 diabetes, BMI and dyslipidemia in families of Northeastern Mexico: A pilot study

“…In the presently analyzed population, rs5218 had a MAF of 0.209 and rs5219 had a MAF of 0.329. Similarly, two previous studies analyzing the Mestizo population of Mexico City were unable to identify an association between rs5219 and T2DM ( 20 , 21 ). In particular, the frequency of the risk allele was shown to be too low to reach the power in order to detect an association ( 20 ).…”

Association of common polymorphisms in the VEGFA and SIRT1 genes with type 2 diabetes-related traits in Mexicans

“…CDKN2A/B genes are expressed in adipocytes and pancreatic islets and play a role in β-cell function and regeneration. The polymorphism rs10811661 located 125 kb upstream of these genes has been identified as a risk allele in a contemporaneous Mayan population [ 25 ] containing lower rates of dispersion and a high predisposition to obesity, diabetes and consanguineous marriage [ 26 ]. Our results showed no statistically significant difference in allele frequency of this variant compared to HapMap and the 1000 Genomes Project, or with any of the traits related to T2D.…”

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

“…Reviewing exact data was occasionally hampered by flaws in some studies, where SNP alleles were not reported, or tables and text have not been in agreement [54,134]. Determining DNA strand specificity and reporting the respective minor and major alleles is easy for A/G, A/C, T/G, and T/C base exchanges.…”

“…A significant association between plasma leptin and rs5219 (G/A, missense variant p.E23K) of potassium channel, inwardly rectifying subfamily J, member 11 (KCNJ11) was found in a population from Yucatan, Mexico [54]. Carriers of the A-allele exhibited higher serum leptin levels.…”