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Metabolic syndrome (MetS) is prevalent in type 2 diabetes (T2D) patients. The comorbidity of MetS and T2D increases the risk of cardiovascular complications. The aim of the present study was to determine the T2D-related genetic variants that contribute to MetS-related components in T2D patients of Chinese ancestry. We successfully genotyped 25 genome wide association study validated T2D-related single nucleotide polymorphisms (SNPs) among 5,169 T2D individuals and 4,560 normal glycemic controls recruited from the Chinese National Diabetes and Metabolic Disorders Study (DMS). We defined MetS in this population using the harmonized criteria (2009) combined with the Chinese criteria for abdominal obesity. The associations between SNPs and MetS-related components, as well as the associations between SNPs and risk for T2D with or without MetS, were subjected to logistic regression analysis adjusted for age and sex. Results showed that the T2D risk alleles of rs243021 located near  BCL11A , rs10830963 in  MTNR1B , and rs2237895 in  KCNQ1  were related to a lower risk for abdominal obesity in T2D patients (rs243021: 0.92 (0.84, 1.00),  P  = 4.42 × 10 −2 ; rs10830963: 0.92 (0.85, 1.00),  P  = 4.07 × 10 −2 ; rs2237895: 0.89 (0.82, 0.98),  P  = 1.29 × 10 −2 ). The T2D risk alleles of rs972283 near  KLF14  contributed to a higher risk of elevated blood pressure (1.10 (1.00, 1.22),  P  = 4.48 × 10 −2 ), while the T2D risk allele of rs7903146 in  TCF7L2  was related to a lower risk for elevated blood pressure (0.74 (0.61, 0.90),  P  = 2.56 × 10 −3 ). The T2D risk alleles of rs972283 near  KLF14  and rs11634397 near  ZFAND6  were associated with a higher risk for elevated triglycerides (rs972283: 1.11 (1.02, 1.24),  P  = 1.46 × 10 −2 ; rs11634397: 1.14 (1.00, 1.29),  P  = 4.66 × 10 −2 ), while the T2D risk alleles of rs780094 in  GCKR  and rs7903146 in  TCF7L2  were related to a lower risk of elevated triglycerides (rs780094: 0.86 (0.80, 0.93),  P  = 1.35 × 10 −4 ; rs7903146: 0.82 (0.69, 0.98),  P  = 3.18 × 10 −2 ). The genotype risk score of the 25 T2D-related SNPs was related to a lower risk for abdominal obesity ( P   trend  = 1.29 × 10 −2 ) and lower waist circumference ( P  = 2.20 × 10 −3 ). Genetic variants of  WFS1 ,  CDKAL1 ,  CDKN2BAS ,  TCF7L2 ,  HHEX ,  KCNQ1 ,  TSPAN8/LGR5 ,  FTO , and  TCF2  were associated with the risk for T2D with MetS, as well as the risk for development of T2D with at least one of the MetS components ( P  < 0.05). In addition, genetic variants of  BCL11A ,  GCKR ,  ADAMTS9 ,  CDKAL1 ,  KLF14 ,  CDKN2BAS ,  TCF7L2 ,  CDC123/CAMK1D ,  HHEX ,  MTNR1B , and  KCNQ1  contributed to the risk for T2D without MetS ( P  < 0.05). In conclusion, these findings highlight the contribution of T2D-related genetic loci to MetS in a Chinese Han population. The study also provides insight into the pleotropic effects of genome-wide association loci of diabetes on metabolic regulation.

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The Association of Type 2 Diabetes Loci Identified in Genome-Wide Association Studies with Metabolic Syndrome and Its Components in a Chinese Population with Type 2 Diabetes