Abstract
BackgroundMany susceptible loci for type 2 diabetes mellitus (T2DM) have recently been identified from Caucasians through genome wide association studies (GWAS). We aimed to determine the association of 11 known loci with T2DM and impaired glucose regulation (IGR), individually and in combination, in Chinese.Methods/Principal FindingsSubjects were enrolled in: (1) a case-control study including 1825 subjects with T2DM, 1487 with IGR and 2200 with normal glucose regulation; and (2) a prospective cohort with 734 non-diabetic subjects at baseline. The latter was followed up for 3.5 years, in which 67 subjects developed T2DM. Nineteen single nucleotide polymorphisms (SNPs) were selected to replicate in both studies. We found that CDKAL1 (rs7756992), SLC30A8 (rs13266634, rs2466293), CDKN2A/2B (rs10811661) and KCNQ1 (rs2237892) were associated with T2DM with odds ratio from 1.21 to 1.35. In the prospective study, the fourth quartile of risk scores based on the combined effects of the risk alleles had 3.05 folds (95% CI, 1.31–7.12) higher risk for incident T2DM as compared with the first quartile, after adjustment for age, gender, body mass index and diabetes family history. This combined effect was confirmed in the case-control study after the same adjustments. The addition of the risk scores to the model of clinical risk factors modestly improved discrimination for T2DM by 1.6% in the case-control study and 2.9% in the prospective study.Conclusions/SignificanceOur study provided further evidence for these GWAS derived SNPs as the genetic susceptible loci for T2DM in Chinese and extended this association to IGR.
Highlights
Type 2 diabetes mellitus (T2DM) is one of the fastest growing diseases with a major impact on morbidity and premature mortality worldwide
The findings support the individual associations of CDKN2A/2B, SLC30A8, CDKAL1 and KCNQ1 with type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) in a case-control study
We found that the combination of the risk alleles demonstrated a more robust association with T2DM and IGR than a single one after adjustment for the common clinical risk factors, such as age, gender, BMI and diabetes family history in both case-control and prospective studies
Summary
Type 2 diabetes mellitus (T2DM) is one of the fastest growing diseases with a major impact on morbidity and premature mortality worldwide. A rapid increase in the prevalence of T2DM and impaired glucose regulation (IGR) has been observed in China in recent decades [1]. T2DM is a complex disorder characterized by impaired insulin sensitivity and pancreatic b cell dysfunction; and is involved in complicated interactions between genetic variants and environmental factors. Several genome wide association studies (GWAS) and replicated studies on the common genetic variants in T2DM have been reported in several large white populations [2,3,4,5] since the first GWAS [6] published. Many susceptible loci for type 2 diabetes mellitus (T2DM) have recently been identified from Caucasians through genome wide association studies (GWAS). We aimed to determine the association of 11 known loci with T2DM and impaired glucose regulation (IGR), individually and in combination, in Chinese
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