Abstract
BackgroundRecent genome-wide association studies have identified a number of common variants associated with fasting glucose homeostasis and type 2 diabetes in populations of European origin. This is a replication study to examine whether such associations are also observed in Chinese Hans.MethodsWe genotyped nine variants in or near MADD, ADRA2A, CRY2, GLIS3, PROX1, FADS1, C2CD4B, IGF1 and IRS1 in a population-based cohort including 3,210 unrelated Chinese Hans from Beijing and Shanghai.ResultsWe confirmed the associations of GLIS3-rs7034200 with fasting glucose (beta = 0.07 mmol/l, P = 0.03), beta cell function (HOMA-B) (beta = −3.03%, P = 0.009), and type 2 diabetes (OR [95%CI] = 1.27 [1.09–1.49], P = 0.003) after adjustment for age, sex, region and BMI. The association for type 2 diabetes remained significant after adjusting for other diabetes related risk factors including family history of diabetes, lipid profile, medication information, hypertension and life style factors, while further adjustment for HOMA-B abolished the association. The A-allele of CRY2-rs11605924 was moderately associated with increased risk of combined IFG/type 2 diabetes (OR [95%CI] = 1.15[1.01–1.30], P = 0.04). SNPs in or near MADD, ADRA2A, PROX1, FADS1, C2CD4B, IGF1, and IRS1 did not exhibit significant associations with type 2 diabetes or related glycemic traits (P≥0.10).ConclusionsIn conclusion, our results indicate the associations of GLIS3 locus with type 2 diabetes and impaired fasting glucose in Chinese Hans, partially mediated through impaired beta-cell function. In addition, we also found modest evidence for the association of CRY2-rs11605924 with combined IFG/type 2 diabetes.
Highlights
Genome-wide association studies (GWAS) have achieved great success in identifying common genetic variants associated with type 2 diabetes
A large genome-wide metaanalysis of data from 21 GWAS in populations of European origin identified a common variant near IGF1 associated with hyperinsulinemia and insulin resistance (HOMA-IR), and nine novel loci influencing fasting glucose [6]
Of the nine variants genotyped in this study, GLIS3-rs7034200 showed significant associations with fasting glucose (b = 0.07 mmol/l, P = 0.03) and HOMA-B (b = 23.03%, P = 0.009), but not with BMI, HbA1c or Homeostasis model assessment of insulin resistance (HOMA-IR) (P$0.20) (Table 2)
Summary
Genome-wide association studies (GWAS) have achieved great success in identifying common genetic variants associated with type 2 diabetes. A large genome-wide metaanalysis of data from 21 GWAS in populations of European origin identified a common variant near IGF1 associated with hyperinsulinemia and insulin resistance (HOMA-IR), and nine novel loci (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, PROX1, SLC2A2, C2CD4B) influencing fasting glucose [6]. Recent genome-wide association studies have identified a number of common variants associated with fasting glucose homeostasis and type 2 diabetes in populations of European origin. This is a replication study to examine whether such associations are observed in Chinese Hans
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