rs5215

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 comprehensive review examines the association between type 2 diabetes mellitus (T2DM) and multiple myeloma (MM) risk. Genetic variants linked to T2DM show opposite associations with MM compared to diabetes GWAS: variants like CDKN2A-2B rs2383208, IGF1 rs35767, KCNQ1 rs2237892, and MADD rs7944584 increase MM risk, while FTO rs8050136, KCNJ11 rs5215/rs5219, LTA rs1041981, and THADA rs7578597 decrease risk. The IGF1 rs35767 promoter polymorphism is strongly associated with MM risk via cell proliferation mechanisms. A meta-analysis of 20 observational studies (>3 million participants) found T2DM patients had OR=1.53 (95% CI, 1.30-1.81) for MM, and MetS patients had OR=1.39 (95% CI, 1.17-1.64), mediated through insulin resistance, hyperinsulinemia, inflammatory cytokines (IL-6, TNF-α, IL-1β), dyslipidemia, and acidosis pathways.

This case-control study analyzed 7 SNPs in 6 genes previously associated with type 2 diabetes (T2DM) in 235 kidney transplant patients medicated with tacrolimus to determine their effect on new-onset diabetes after transplantation (NODAT). While no individual SNP showed significant association with NODAT, patients carrying >7 of the 14 'diabetogenic' alleles had significantly higher NODAT risk (OR 2.17, 95% CI 1.18–3.99, p=0.015), particularly for late-onset NODAT (OR 1.37 per allele, 95% CI 1.05–1.78, p=0.017).

This GWAS of fasting glucose in the ARIC study examined 5,782-8,372 individuals across four longitudinal visits and identified five genomic regions significantly associated with fasting glucose (p < 5×10⁻⁸): GCKR, G6PC2, GCK, SLC30A8, and MTNR1B. The study demonstrated that averaging fasting glucose measures across visits improved statistical power and detected additional signals (GCKR rs780094, SLC30A8 rs13266634) not visible in single-visit analyses. Analysis of candidate SNPs revealed significant interactions with diabetes status: associations with fasting glucose were stronger in non-diabetic individuals than in those with prevalent diabetes for multiple SNPs including rs10830963 (MTNR1B), rs560887 (G6PC2), rs4607517 (GCK), and rs780094 (GCKR).

The HERITAGE Family Study examined eight type 2 diabetes susceptibility variants in 481 sedentary individuals undergoing 20-week endurance training. PPARG rs1801282 (Pro12Ala) was the only significant finding: Ala carriers showed greater improvements in glucose tolerance (p=0.0008), glucose effectiveness (p=0.004), and disposition index (p=0.003) in response to exercise training, though no associations were found with other recently identified GWAS variants.

This case-control study in 869 Korean women with gestational diabetes mellitus (GDM) and 632 non-diabetic controls examined whether type 2 diabetes-associated genetic variants discovered in recent GWAS are also associated with GDM. Multiple variants showed significant associations with GDM, including rs7756992 and rs7754840 in CDKAL1 (OR 1.55, p=4.17×10⁻⁹), rs10811661 in CDKN2A-CDKN2B (OR 1.49, p=1.05×10⁻⁷), variants in HHEX, rs4402960 in IGF2BP2 (OR 1.18, p=0.03), rs13266634 in SLC30A8 (OR 1.24, p=0.005), and rs7903146 in TCF7L2 (OR 1.58, p=0.038).

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).

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 case-control association study in 864 Japanese type 2 diabetes patients and 864 controls confirmed that three SNPs in HHEX (rs5015480 OR=1.46, rs7923837 OR=1.40, rs1111875 OR=1.30) were significantly associated with type 2 diabetes across ethnic groups. SNPs in FTO, CDKAL1, CDKN2B, and SLC30A8 showed nominal associations, while several SNPs were associated with impaired pancreatic beta cell function measured by HOMA-beta index.