Type 2 diabetes and polymorphisms on chromosome 9p21: A meta-analysis

D. Cugino, F. Gianfagna, I. Santimone, G. De Gaetano, M. B. Donati, L. Iacoviello, A. Di Castelnuovo

Research output: Contribution to journalArticlepeer-review

Abstract

Background and aims: Genome-Wide Association Studies found some variants on chromosome 9p21 associated with type 2 diabetes (T2D). We performed a meta-analysis to estimate strength, accuracy and feature of the association of polymorphisms in 9p21 with T2D. Methods and results: Articles were retrieved screening electronic databases and cross references. Twenty-two publications were identified, for a total of 38,455 T2D patients and 60,516 controls. Twenty-one studies investigated the role of the SNP rs10811661; in some studies three additional SNPs (rs564398, rs10757278, rs1333040) were genotyped. Population attributable risk (PAR) was computed as: risk allele frequency*(OR-1)/OR, using the per-allele odds ratio (OR).The risk allele (T) of rs10811661 was associated with T2D in most of the studies. In meta-analysis the overall per-allele OR was 1.24 (95% CI: 1.21-1.27; P <10-15), with no difference according to ethnicity (P = 0.45), and low heterogeneity (P = 0.040) across studies partly explained by sample size. Modeling of inheritance suggested an additive effect of the T allele. PAR of T2D related to this polymorphism was 15% for Caucasians and 13% for Asians. The overall odds ratio for the T allele of the SNP rs564398 was 1.08 (95% CI: 1.05-1.12; PAR = 6%). The other SNPs showed negligible associations. Conclusions: This meta-analysis provides accurate and comprehensive estimates of the association of some genetic variants at chromosome 9p21 and T2D. A relatively small but significant role of the T allele of the rs10811661 SNP in increasing by 21-27% the risk of T2D in an additive way was apparent.

Original languageEnglish
Pages (from-to)619-625
Number of pages7
JournalNutrition, Metabolism and Cardiovascular Diseases
Volume22
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

  • Chromosome 9p21
  • Genetic polymorphisms
  • Meta-analysis
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

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