| Objective:Aim to study the association of two candidate polymorphisms (rs151290 and rs2237897) in the Potassium Voltage-gated channel,KQT-like subfamily,member 1 (KCNQ1) gene with type 2 diabetes mellitus and diabetic nephropathy.Methods:Selected 624 individuals in Yunnan Han population, including 336 T2DM cases{including 171 diabetic non-nephropathy (NDN) patients,153 diabetic nephropathy (DN) cases [112 microalbuminuria (DN1) patients and 41 patients with macroalbuminuria group (DN2)]}and 288 healthy normal controls (NC), were investigated for candidate SNPs in KCNQ1 and association with type 2 diabetes mellitus and diabetic retinopathy.SNPs rs151290 and rs2237897 were genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP) or TaqMan genotyping allelic discrimination assay, respectively. Cilinical and biochemical characteristics were compared among groups accoring to different genotype or allele. The fasting plasma GLP-1 was measured by Enzyme linked immunosorbent assay (EIASA) method in 145 individuals.Results:1. BMI, WHR, SBP, DBP and ALT were higher in the T2DM patients than those in NC group; while HOMA-IR, HDL-C andβ-cell function index were lower among T2DM group than in NC group. DM duration, SBP, HbAlc was higher in DN patients than the NDN patients,120 minutes C-peptide and isletβcell function index of DN patients were lower than the NDN patients.2. The allele C frequency of rs151290 in the T2DM group was significantly higher than that in the control group (62.5%vs.67.4%, OR=1.12[1.008-1.318],P=0.04); The distribution of AA and AC genotype among the T2DM patients was significantly lower than NC controls (OR=1.216[1.036-1.428]P=0.017), and the association was remained after adjustment for age、sex and BMI (P=0.036).The C allele frequency of rs2237897 in the T2DM group was significantly higher than that in the control group (64%vs.70%, OR=1.331 [1.042-1.701] P=0.02); The distribution of CT and TT genotype in the T2DM patient was significantly lower than NC controls (OR=1.34 [1.141-1.574] P<0.001), and the association was remained after adjustment for age、sex and BMI (P<0.001).3.The A allele frequencies of rs151290 among NDN, DN1 and DN2 groups were 31.3%,33.5% and 40.2%, respectively; The difference reached significance (P= 0.048). The distribution of AA+AC genotype in DN subjects was significantly higher than that in NDN controls (OR=1.250 [1.002-1.558] P=0.039), and the association was remained after adjustment for age、sex and BMI (P= 0.006). The T allele frequencies of rs2237897 in the NDN group, DN1 and DN2 groups were 27%, 33% and 32%, respectively. The difference between the three groups was not significant (P=0.265); The T allele frequencies of rs2237897 in NDN and DN patients were 27% and 33%, respectively, but the difference was not statistically significant (P=0.09).4. In NC group, compared with AA carriers (AA), CC+AC carriers of rs151290 was associated with higher SBP (+8.36mmHg,P= 0.011), higher DBP(+5.23mmHg,P =0.006), while AA+AC carriers of rs151290 was associated with higher urinary albumin (+3.614ug/ml,P=0.002) than CC carriers in T2DM patient. In the DN patient, compared with AA carriers (AA), CC+AC carriers of rs151290 was associated with higher HDL-C (+0.184mmol/l, P=0.037) and compared with CC carriers, AA+AC carriers of rs151290 was associated with high 120 minutes of insulin (+14.97pmol/l, P=0.011). In T2DM patients, compared with CC carriers of rs2237897, CT+TT carriers was associated with high homocysteine (+3.614umol/l, P=0.002). 5. No significant association was found between two candidate SNPs (rs151290 and rs2237897) and the level of fasting plasma GLP-1 among NC and T2DM group, DN and NDN group (all the P> 0.05).6.Binary Logistic regression analysis showed that risk factors of DN in T2DM patients were age, DM duration, SBP, HbAlc, fructosamine (FA).Conclusions:1. KCNQ1 gene SNPs rs151290 and rs2237897 were susceptibility loci of T2DM in Chinese Han individules.2. In T2DM group, A allele was more frequent in DN cases than NDN controls, suggesting rs151290 was related to the pathogenesis of DN.However, significant association between DN and rs2237897 was not found.3. KCNQ1 gene might be related with hgher blood pressure in norml controls and dyslipidemia in T2DM cases.4. No correlation between KCNQ1 gene and fasting plasma GLP-1 was found in this study.5. Age, DM duration, systolic blood pressure (SBP), glycosylated hemoglobin (HbAlc%) And other factors were closely related the incidence and development of DN. |
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