Relationship Between Glucokinase Regulatory Protein Pro446Leu Gene Polymorphism And Type 2 Diabetes Mellitus In People Of Hui Nationality In Gansu Province

Objective1.To investigate the distribution of glucokinase regulatory protein (GCKR) gene(pro446Leu, rs1260326) polymorphism in people of Hui nationality in Gansu province.2.To investigate the association with GCKR gene pro446Leu polymorphism and type 2 diabetes mellitus (T2DM), insulin resistance, plasma glucose, blood lipid,blood pressure and uric acid etc in people of Hui nationality in Gansu province.MethodsWe conducted a case-control study with 178 patients (90 males and 88 females) with T2DM and 207 normal controls (102 males and 105 females) age from 31 to 83(at an average age of 54.2±11.2 years).T2DM was defined according to world hearth organization (WHO) criteria.,Subjects with cardiovascular disorders,acute or chronic hepatopathy and nephr-opathy, as well as other endocrine dieases were excluded. Anthropometric parameters including height,weight,waistline,hip circumference,blood pressure, fasting plasmaglucose (FPG), fasting insulin(FINS),blood fat, uric acid, waist hip ratio(WHR),body mass index (BMI) and insulin resistance index (HOMA-IR).All subjects were not genetically related.The subjects were genotyped for the single nucleotide polymorphisms (SNP) pro446Leu in exon 15 of GCKR gene by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). Excel was used to build database.SPSS 11.0 was used for analyses.Results1.The genotype frequencies of CC,CT,TT were 0.491,0.306,0.203 and 0.613,0.296,0.091 in normal control group and T2DM group, respectively;2.Allele frequencies of C,T were 0.643,0.764 and 0.357,0.236 in normal control group and T2DM group, respectively;There were significant differences in genotype and frequencies of allele in GCKR pro446Leu polymorphism between normal control group and T2DM group (P<0.05); 3.Compared with the control subjects, T2DM patients had significantly higher FPG, FINS,HOMA-IR, triglyceride (TG), systolic blood pressure(P<0.05).However, there were no significant differences in age, waist circumference, hip circumference, WHR, BMI, diastolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and uric acid levels between the two groups(P>0.05);4. Morever,the levels of serum FPG and HOMA-IR of T-allele carriers were lower while TG was higher than that of C allele carriers (P<0.05).ConclusionGCKR gene pro446Leu polymorphism was existed in people of Hui nationality in Gansu province.These findings indicate that the GCKR SNP pro446Leu might be significantly associated with T2DM, insulin resistance and blood lipid levels.however, There were no associations with blood pressure and uric acid.Hereby,T-allele seems to be a protective factor of T2DM in people of Hui nationality in Gansu province.