| Objective Microvascular complications of diabetes?MVCD?mainly consists of diabetic nephropathy?DN?and diabetic retinopathy?DR?.DN and DR are leading causes of end stage renal failure and blindness in diabetes patients.Previous studies showed that the duration of diabetes and the plasma glucose level are MVCD risk factors,however,some diabetes patients with severe hyperglycemia never suffered from MVCD.On the other hand,many diabetes patients with well controlled blood glucose have developed MVCD.Many studies have found family aggregation and significant increased risks in siblings of MVCD,suggested that genetic factor played an important role in the etiology of MVCD.To study associations among single nucleotide polymorphisms?SNPs?of candidate genes and microvascular complications of type 2 diabetes,we performed case/control association studies for MVCD candidate genes in Han Chinese type 2 diabetes?T2DM?patients and never diabetic controls.Methods We have recruited 1474 unrelated Han Chinese T2DM patients in Tianjin.Nine hundred nine?909?individuals with more than 57 years old and normal blood glucose levels were collected as non-diabetic controls.Subjects were collected from General Hospital of Tianjin Medical University,Metabolic Disease Hospital of Tianjin Medical University,Nankai University People's Hospital,and Tianjin Medical University Eye Center.Six hundred ninety-nine?699?patients have DN,335 have non-Proliferative Diabetic Retinopathy?NPDR?,93 have Proliferative Diabetic Retinopathy?PDR?.One hundred ninety one?191?patients have both DN and DR.One hundred ninety three?193?patients have T2DM history for more than 10 years but have never developed DR or DN.Patient's general information and clinical characteristics were collected,including gender,age,height,weight,biochemistry and lipid profiles,and fasting plasma glucose.Genomic DNA samples were extracted from peripheral whole blood samples using the high-salt method.Eighty-five?85?SNPs in 55 candidate genes were genotyped by matrix-assisted laser desorption time-of-flight mass spectrometry.Data checking and statistical analyses were performed by SPSS17.0.Association study were carried out by PLINK.ResultsWe employed a 3-step case-control study for T2DM and MVCD:?1?We used all 1474 T2DM patients as cases,909 non-diabetic individuals?>57 years old,with normal blood glucose?as controls.Association analyses for T2DM showed association among candidate gene SNPs and T2DM,including rs 10811661 of the CDKN2A/B gene(P=9.90×10-7),rs1526167 of the TOX gene?P=1.22×10-6?,rs4402960 of the IGF2BP2 gene(P=6.68×10-4),rs7660895 of the SLC2A9 gene(P=2.34×10-4),rs6856526 of the LPHN3 gene(P=1.14×10-3),and rsl3266634 of the SLC30A8 gene?P=0.O0?.?2?Subjects with DN,DR,PDR,and MVCD were selected as cases,individuals with normal plasma glucose levels?age>57?and patients with more than 10 years of T2DM history but without DR or DR were chosen as controls.Association analyses of dichotomic variables showed that the rs10811661 of the CDKN2A/B gene was associated with DN(P=1.87×10-5),DR(P=2.19×10-4),MVCD?P=2.54×10-6?and PDR(P=8.34×10-4);The SLC2A9 gene SNP rs7660895 was associated with DN(P=1.10×10-3),DR(P=1.37×10-4)and MVCD(P=4.56×10-4);The CDKAL1 gene SNP rs7756992 was associated with DN(P=9.41×10-3),DR?P=0.04?,MVCD(P=5.92×10-3)and PDR?P=0.02?;The TOX gene SNP rs1526167 was associated with DN(P=2.19×10-3),DR?P=0.01?and MVCD(P=2.24×10-3);The SLC30A8 gene SNP rs13266634 was associated with DN(P=6.20×10-3),DR?P=0.04?,MVCD(P=2.29×10-3)and PDR?P=0.04?.?3?DN,DR,PDR,MVCD patients were selected as cases.Patients with>10 years T2DM history,without DR or DN were chosen as controls.Association analyses of dichotomic variables showed that the rs 1526167 of the TOX gene was associated with DN(P=2.86×10-3),DR(P=7.99×10-3),PDR?P=0.04?and MVCD(P=2.28×10-3);The SNP rs10811661 of the CDKN2A/B gene was associated with DN?P=0.04?,DR?P=0.03?,PDR(P=5.40×10-3)and MVCD?P=0.02?.Conclusions Significant associations were found among SLC2A9,CDKAL1,TOX,SLC30A8 and CDKN2A/B gene SNPs and MVCD in T2DM patients.Significant associations were found among SLC2A9,CDKAL1,TOX,SLC30A8,CDKN2A/B,IGF2BP2 gene SNPs and T2DM.In Han Chinese T2DM patients,TOX and CDKN2A/B gene SNPs were associated with DR,DR,and MVCD. |
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