Research On Relationship Between-23A/T Variation Of Insulin Gene And Early-onset Type 2 Diabetes

OBJECTIVES: Insulin is a uniquehypoglycemic hormone in vivo secreted by islet beta cells.The insulin gene mutation/viariation plays an important role in the occurrence and development of diabetes by influencing the insulin secretion.To explore the relationship between the-23A/T variation of insulin gene(INS)and early-onset type 2 diabetes mellitus(T2DM),which wascarried out in Shanghai Han populationMETHODS: A total of 116 Shanghai Han patients with early-onset T2DM(onset age<40 years old,case group)and 135 non-diabetic controls(age>50 years old,control group)were enrolled.The genotypes of-23A/T for individuals were detected by the PCR-direct sequencing.Frequencies of genotypes and alleles of-23A/T as well as clinical characteristics between the two groups were compared and analyzed.RESULTS: 1)Three genotypes(AA,AT,TT)of-23A/T were detected.AA and A are major genotype and allele of-23A/T respectively.2)The genotype distribution of-23A/T in early-onset T2 DM group or control group was consistent with Hardy-Weinberg equilibrium.3)Compared with the control group,AA genotypic and A allelic frequencies significantly increased in the early-onset T2 DM group respectively(P<0.05 for each).In comprison to subjects with AT or TT genotypes,the risk of incidence of early-onset T2 DM for subjects with AA genotype were significantly increased with OR of 2.77(95%CI,1.19-6.47,P < 0.05).Meanwhile,A allele of-23A/T significantly correlated with early-onset T2 DM with OR of 2.86(95%CI,1.26-6.46,P<0.05).4)In the early-onset T2 DM group,the fasting serum insulin(FINS)and HOMA-B level of subjects with AA genotype was significantly lower than that of subjects with AT genotype(P<0.05 for each).At the same time,the 2hINS level of AA genotype carriers had an increasing tendency(P>0.05).CONCLUSIONS: The A allele of-23A/T variation of INS gene is significantly associated with the fasting serum insulin in early-onset T2 DM of Shanghai Han patients,which is a risk factor for early-onset T2 DM.The-23A/T variation may be a possible genetic marker to predict β-cell failure in the near future in early-onset T2 DM patientsin Chinese.