TOX and CDKN2A/B Gene Polymorphisms Are Associated with Type 2 Diabetes in Han Chinese

Abstract

To study associations between type 2 diabetes (T2DM) candidate genes and microvascular complications of diabetes (MVCDs), we performed case-control association studies for both T2DM and MVCDs in Han Chinese subjects. We recruited 1,939 unrelated Han Chinese T2DM patients and 918 individuals with normal blood glucose levels as nondiabetic controls. Among T2DM patients, 1116 have MVCDs, 266 have a history of T2DM of >10 years but never developed MVCDs. Eighty-two single-nucleotide polymorphisms (SNPs) in 54 candidate genes were genotyped. Discrete association studies were performed by the PLINK program for T2DM and MVCDs. Significant associations were found among candidate gene SNPs and T2DM, including rs1526167 of the TOX gene (allele A, P = 2.85 × 10−9, OR = 1.44). The SNP rs10811661 of the CDKN2A/B gene was also associated with T2DM (allele T, P = 4.09 × 10−7, OR = 1.36). When we used control patients with >10 years of T2DM history without MVCD, we found that the G allele of SNP rs1526167 of the TOX gene was associated with MVCD (nominal P = 4.33 × 10−4). In our study, significant associations were found between TOX and CDKN2A/B gene SNPs and T2DM. The TOX polymorphism might account for the higher risk of T2DM and the lower risk of MVCDs in the Han Chinese population.

Middle-Aged Indians with Type 2 Diabetes Are at Higher Risk of Biological Ageing with Special Reference to Serum CDKN2A

“…Higher risk of high levels of CDKN2A was found in T2DM patients with respect to controls. The previous studies also reported a significant association of CDKN2A locus with T2DM [38,39]. Further, we observed a marked increase in CDKN2A level with the increase in duration of diabetes.…”

Cellular senescence: Implications for metabolic disease

“…Several genome-wide association studies have linked the CDKN2A locus, which encodes p16 INK4a , to type 2 diabetes (Wei et al, 2015; van Hoek et al, 2008; Zeggini et al, 2007; Scott et al, 2007). However, a study examining associations between diabetes-associated polymorphisms and β-cell function and insulin sensitivity in healthy adults failed to identify a relationship between CDKN2A and metabolic impairments (Pascoe et al, 2007).…”

Multivariate Analysis of Anthropometric Traits Using Summary Statistics of Genome-Wide Association Studies from GIANT Consortium

“…Variant rs7842858, has not been reported previously. SNP rs7842858 is located on TOX ( Fig 4 ), which has been reported to be associated with obesity and diabetes [ 20 ].…”

“…In particular, variant rs7842858 has a positive effect on the three traits in males but negative effect in females ( Fig 5 ), which leads to the failure of detection by either conventional single trait meta-analysis or combining the three traits by S Hom . SNP rs7842858 (8:58987111) resides within TOX ( Fig 4 ), which has been reported to be associated with Type 2 Diabetes in Chinese Han population [ 20 ]. It is possible that this variant affects obesity variation and therefore indirectly contributes to Type 2 Diabetes.…”