Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: A case-control study in Han Chinese

Feng Lu, Yun Qian, Huizhang Li, Meihua Dong, Yudi Lin, Jiangbo Du, Yuan Lin, Jian Chen, Chong Shen, Guangfu Jin, Juncheng Dai, Zhibin Hu, Hongbing Shen

Research output: Contribution to journalArticle

16 Scopus citations


Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) on chromosome 6p21.1 and 6p22.3 as type 2 diabetes (T2D) susceptibility loci in the European and Japanese populations. However, these SNPs have not been well evaluated in Chinese population. Here, we performed a case-control study with 2925 T2D cases and 3281 controls in a Chinese population. We used TaqMan OpenArray and Sequenom MassARRAY to genotype the four SNPs (rs4712523, rs7756992, rs4712524 and rs6931514) in CDKAL1 (cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1) at 6p22.3 and one SNP (rs9472138) near vascular endothelial growth factor A (VEGFA) at 6p21.1. All the five SNPs were significantly associated with T2D risk with overall effects (odds ratio, OR) from 1.19 to 1.29 in the additive genetic model (rs6931514: OR=1.29, 95% confidence intervals (95% CI)=1.19-1.39, P=5.6×10-10; rs7756992: OR=1.23, 95% CI=1.15-1.32, P=1.2×10-8; rs4712523: OR=1.25, 95% CI=1.15-1.35, P=3.8×10-8; rs4712524: OR=1.24, 95% CI=1.15-1.35, P=6.8×10-8; rs9472138: OR=1.19, 95% CI=1.05-1.34, P=006). Conditional analysis identified two independent signals (rs6931514 at 6p22.3 and rs9472138 at 6p21.1) that were significantly associated with T2D. Compared with the wild homozygote of rs6931514 and rs9472138, subjects with variant alleles of the two SNPs had increased risk for T2D susceptibility in a dose-response manner (Ptrend=7.4×10-12). Our findings indicated that genetic variants of CDKAL1 and VEGFA on chromosome 6 may contribute to T2D risk in Chinese population, especially for rs9472138 at 6p21.1 identified for the first time to significantly increase the T2D risk in Chinese individuals.

Original languageEnglish (US)
Pages (from-to)320-325
Number of pages6
JournalJournal of Human Genetics
Issue number5
StatePublished - May 1 2012
Externally publishedYes


  • CDKAL1
  • genome-wide association study
  • polymorphism
  • type 2 diabetes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Genetic variants on chromosome 6p21.1 and 6p22.3 are associated with type 2 diabetes risk: A case-control study in Han Chinese'. Together they form a unique fingerprint.

Cite this