rs10885406

A literature review of 70 studies examining single nucleotide polymorphisms (SNPs) associated with obesity in Mexican populations published 2011-2021. The authors identified SNPs with differential behavior in Mexican compared to Caucasian populations, including rs17782313 (MC4R), rs6548238 (TMEM18), rs6265 (BDNF), rs7498665 (SH2B1), and notably rs6232 (PCSK1) associated with early-onset obesity in Mexican youth. The review emphasizes ethnicity-dependent genetic effects on BMI heritability (40-70%) and highlights genes involved in cholesterol metabolism and adipokine signaling pathways.

This retrospective pharmacogenomic analysis of 961 type 2 diabetes patients from four 24-week phase III trials examined whether TCF7L2 gene variants influence response to linagliptin (DPP-4 inhibitor). Linagliptin lowered HbA1c across all rs7903146 genotypes (CC: -0.82%, CT: -0.77%, TT: -0.57%), with significantly reduced response in homozygous risk carriers (TT vs CC: difference ~0.26%, p=0.0182), indicating that diabetes susceptibility genes contribute to inter-individual treatment response variability.

This study examined TCF7L2 variants in 2,512 Framingham Heart Study participants and confirmed that rs7903146 T risk allele associates with increased fasting plasma glucose (p=0.01) and a 23.5% higher proinsulin/insulin ratio (p=1×10⁻⁷) compared to C/C homozygotes, supporting the hypothesis of impaired beta cell insulin processing. However, the authors found no association between TCF7L2 haplotype A and obesity measures (BMI p=0.98), suggesting previous positive associations were likely due to ascertainment bias.

This case-control study examined three TCF7L2 SNPs (rs7901695, rs7903146, rs12255372) in 706 Spanish individuals (180 with type 2 diabetes) and found that the T allele of rs7903146 was significantly associated with increased type 2 diabetes risk (OR 1.29, 95% CI 1.06-1.57, p=0.01). The risk alleles were also associated with an elevated proinsulin:insulin ratio after oral glucose tolerance testing, suggesting TCF7L2 involvement in insulin synthesis and processing rather than just secretion.

This study examined whether genetic markers (HLA-DQB1, PTPN22, INS VNTR, TCF7L2) could distinguish autoimmune from non-autoimmune diabetes in 1,642 young (15-34 years) and 1,619 middle-aged (40-59 years) Swedish diabetic patients. TCF7L2 rs7903146 CT/TT genotypes were significantly more common in young GADA-negative than GADA-positive patients (53% vs 43%; p=0.0004), suggesting TCF7L2 variants help differentiate type 2 diabetes from autoimmune diabetes in young but not middle-aged patients.