rs7901695

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.

Of 40 SNPs previously associated with type 2 diabetes, 19 (48%) introduce or remove CpG sites. In 84 human pancreatic islet donors, all 16 analyzed CpG-SNPs showed statistically significant differential DNA methylation (p≤2.3×10⁻⁵). Several CpG-SNPs including rs391300 (SRR), rs5945326 (DUSP9), rs11708067 (ADCY5), rs5015480 (HHEX), rs13266634 (SLC30A8), rs1801214 (WFS1), rs564398 (CDKN2A), and rs2237895 (KCNQ1) were associated with differential gene expression, alternative splicing, or hormone secretion, suggesting DNA methylation-mediated mechanisms linking genetic variants to type 2 diabetes pathogenesis.

This case-control study investigated 25 T2DM-associated SNPs in a multi-ethnic Hawaiian cohort (291 GDM cases, 734 controls) and found ethnicity-specific associations with gestational diabetes. Key findings in Filipinos included rs1113132 (EXT2, OR=1.52, p=0.028), rs1111875 (HHEX, OR=1.5, p=0.047), rs2237892 (KCNQ1, OR=0.49, p<0.001), rs10830963 (MTNR1B, OR=0.63, p=0.025), and rs13266634 (SLC30A8, OR=0.58, p=0.011). In Japanese women, rs4402960 (IGFBP2, OR=0.5, p=0.031) and rs2237892 (KCNQ1, OR=0.5, p=0.03) were significant. Pacific Islanders showed associations with rs10830963 (MTNR1B, OR=0.52, p=0.037) and rs13266634 (SLC30A8, OR=2.43, p=0.03). No SNPs showed consistent associations across all three ethnic groups.

This study tests the thrifty genotype hypothesis by examining 17 confirmed type 2 diabetes susceptibility loci and 13 obesity-susceptibility loci for signatures of positive selection. Using ancestral/derived allele analysis, integrated haplotype scores (iHS), and population differentiation (FST), the authors found limited evidence supporting the thrifty genotype hypothesis. Only rs7901695 at TCF7L2 showed notably elevated FST values (0.579 between JPT+CHB and YRI populations), and FTO showed the strongest selection signal among obesity loci (iHS=1.991).

This replication study tested 22 candidate SNPs for association with late-onset Alzheimer's disease in 1,009 cases and 1,010 controls of Caucasian descent. While the primary analysis found no significant associations with AD risk, the study identified notable associations with age-at-onset (rs2074877 in MYH13, p=0.00196) and disease duration (rs41271951 in CTSS and rs41310885 in FAM63A, p=0.006 and p=0.0014, respectively).

Case-control study of 273 T2DM patients and 343 controls in the Tunisian population examined three GLUT1 SNPs (rs710218, rs841847, rs841853). The XbaI SNP (rs841853) GT genotype conferred increased T2DM risk (OR=2.4), and the TAT haplotype combining all three SNPs showed the strongest association with T2DM susceptibility (OR=3.4).

This study examined whether TCF7L2 SNPs (rs7903146, rs12255372, rs7901695, rs11196205, rs7895340) are associated with cardiovascular disease (CVD) and mortality in the ARIC cohort of 13,369 participants. The T-allele of rs7903146 was not significantly associated with incident coronary heart disease, ischemic stroke, CVD, or all-cause mortality in the full cohort or when stratified by race. A weak association with incident CHD was observed in whites with prevalent diabetes (HR = 1.21, p = 0.04) but not in blacks, suggesting TCF7L2's increased health risk is specific to diabetes rather than general cardiovascular disease.

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 investigated whether TCF7L2 gene variants associated with type 2 diabetes in European populations also confer risk in Japanese populations. The SNP rs7903146 showed significant association with type 2 diabetes in combined Japanese samples (n=1,997; OR=1.69, 95% CI 1.21–2.36, p=0.002), demonstrating that TCF7L2 is a common type 2 diabetes susceptibility gene across ethnic groups.

This association study of 1,110 non-diabetic participants examined TCF7L2 gene polymorphisms (rs7903146, rs12255372, rs7901695) and found that risk allele carriers have specifically impaired GLP-1-induced insulin secretion (p<0.02 for rs7903146 and rs12255372), consistent with a defect in the GLP-1 signaling pathway in pancreatic beta cells rather than reduced GLP-1 secretion. This functional deficit provides a mechanistic explanation for the increased type 2 diabetes risk conferred by these variants.

This replication study examined the association of TCF7L2 polymorphisms with type 2 diabetes in a Japanese population of 1,630 patients and 1,064 controls. All four tested SNPs (rs12255372, rs7903146, rs7901695, rs11196205) were significantly associated with type 2 diabetes, with rs12255372 showing the strongest association (OR=1.70, 95% CI=1.20-2.41, p=0.0024). The risk allele frequencies were substantially lower in the Japanese population compared to white populations, suggesting ethnic differences in genetic susceptibility to type 2 diabetes.