Genetic variants at 10q23.33 are associated with plasma lipid levels in a Chinese population

Abstract

Plasma lipid abnormalities are implicated in the pathogenic process of type 2 diabetes. The IDE-KIF11-HHEX gene cluster on chromosome 10q23.33 has been identified as a susceptibility locus for type 2 diabetes. We hypothesized that genetic variants at 10q23.33 may be associated with plasma lipid concentrations. Seven tagging single nucleotide polymorphisms (SNPs: rs7923837, rs2488075, rs947591, rs11187146, rs5015480, rs4646957 and rs1111875) at 10q23.33 were genotyped in 3,281 subjects from a Han Chinese population, using the TaqMan OpenArray and Sequenom MassARRAY platforms. Multiple linear regression analyses showed that SNP rs7923837 in the 3′-flanking region of HHEX was significantly associated with triglyceride levels (P = 0.019, 0.031 mmol/L average decrease per minor G allele) and that rs2488075 and rs947591 in the downstream region of HHEX were significantly associated with total cholesterol levels (P = 0.041, 0.058 mmol/L average decrease per minor C allele and P = 0.018, 0.063 mmol/L average decrease per minor A allele, respectively). However, the other four SNPs (rs11187146, rs5015480, rs4646957 and rs1111875) were not significantly associated with any plasma lipid concentrations in this Chinese population. Our data suggest that genetic variants in the IDE-KIF11-HHEX gene cluster at 10q23.33 may partially explain the variation of plasma lipid levels in the Han Chinese population. Further studies are required to confirm these findings in other populations.

Genetic polymorphisms of diabetes‐related genes, their interaction with diabetes status, and breast cancer incidence and mortality: The Long Island Breast Cancer Study Project

“…In this population-based sample, of the 143 diabetes risk variants genotyped, 12 SNPs were associated with the risk of developing BC, three with all-cause mortality, and three with BC-specific mortality, in additive genotype models at an alpha of 0.05, but none were statistically significant at the Bonferroni-corrected alpha of 0.0003. The top three most significant SNPs associated with BC risk included: rs4876369, an intron variant of SLC30A8 (solute carrier family 30 member 8), which encodes a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles; 35 rs11187146, an intergene variant in the IDE - KIF11 - HHEX gene cluster at 10q23.33 36 ; and rs1333049, an intergene variant in the cyclin-dependent kinase inhibitor 2A/B ( CDKN2A/B ) locus at 9p21.3, hypothesized to play a pivotal role in the development of cardiovascular disease by altering the dynamics of vascular cell proliferation. 37,38 ORs per allele increase for the 12 statistically significant SNPs ranged from 1.14 to 1.34 for those positively associated with BC and from 0.81 to 0.83 for those inversely associated with BC risk.…”

Unraveling the Influence of HHEX Risk Polymorphism rs7923837 on Multiple Sclerosis Pathogenesis

“…The studied HHEX polymorphism rs7923837 has been significantly associated with triglyceride levels by multiple linear regression analyses, and two other SNPs in the downstream region of the gene with total cholesterol levels [ 15 ]. Moreover, genome-wide association studies identified noncoding SNPs associated with type 2 diabetes and obesity in linkage disequilibrium (LD) blocks encompassing the HHEX gene [ 16 , 17 , 18 ].…”