An Association Between Type 2 Diabetes Mellitus And The Single Nucleotide Polymorphisms Of MT-4 And MT-1X Gene

Diabetes mellitus (DM) is a chronic metabolic disorder which can be dividedinto two major subclasses: insulin-dependent diabetes mellitus (IDDM), alsoknown as type 1 diabetes, and non-insulin-dependente diabetes mellitus, alsoknown as type 2 diabetes mellitus (T2DM). T2DM accounts for 90%-95% of allthe diabetes patients. Recent years the incidence of DM has been growingrapidly in China with a current number of diabetes patients over 30 million. Thetreantments for DM and its complications cost a lot which has become a heavyeconomic burden to our society. It is urgent to identify the etiology of DM so asto prevent it. DM is generally accepted as a multiple genetic disease with a closeassociation with obesity. Metallothionein(MT)is an antiperoxidant protein which mediates metalmetabolism. It has been proved to be related to the development of T2DM. In theT2DM model induced by Steptozotocin (STZ), the MT-overexpressed transgenicmice were found to have a lower glucose level compared to control mice.Experiments in vitro indicated that MT could antagonize pancreatic B cell injuryinduced by STZ. MT can also counteract the oxidant injury caused by glucagon.Recently MT has been proved to be associated with obesity which is a high riskfactor for T2DM. In addition, the linkage studies have found that ras relatedassociated with diabetes (RRAD) loci were located on chromosome 16q22,while MT gene family members were on 16q13 within 10 cM distance fromRRAD loci. Therefore it is possible to find susceptibility genes for T2DM on thisregion by screening SNPs.The present study selected the T2DM patients and unrelated heathy controlindividuals as objectes from Han Chinese in North China. The PCR-RFLPmethod was adopted to detect the genotypes of SNPs on MT gene. Thegoodness-of-fitness χ2 test was used to detect whether the genotype frequencydistribution fit the law of Hardy-Weinberg genetic equilibrium. The differencesof alleic gene and genotype distribution beween T2DM and control group weredetected by χ2 test. All the tests were analyzed by SPSS.The present study detected two SNPs, MT-4 gene rs666636 locus andMT-1X gene rs4531729 locus. For MTs rs666636 locus, 162 T2DM patients(male 81 and female 81, respectively) and 190 control individuals (male 95and female95, respectivley). All the objectes in both case and control group wereaged 39-69. For MT-1X gene rs4531729 locus, 132 cases (male 63 and female69, respectively) and 137 healthy individuals (male 63 and female 74,respectivley) were tested. All the objects were aged 39-69. The genotypesdistribution for these two SNPs in general case and control group, male case andcontrol group, female case and control group were all in Hardy-Weinbergequilibrium by gooness-of-fitness χ2 test ( P > 0.05). The χ2 test showed that thefrequency distributions of the alleic gene and genotype for both MT-4 geners666636 locus and MT-1X gene rs4531729 were found no significantdifferences between the T2DM group and control group ( P > 0.05). Stratified bysex for both MT-4 gene rs666636 locus and MT-1X gene rs4531729 locus,frequency distributions of alleic gene and genotypes of MT-4 gene rs666636locus failed to show remarkable differences between the female case group andfemal control group, male case and male control group. Same negative resultswere found in MT-1X gene rs4531729 locus ( P > 0.05). All the above suggestedthat MT gene polymorphism may have no association with T2DM.