DGAT1 Gene Polymorphism In Chinese Families With Type 2 Diabetes

ObjectiveA combination of genetic and environmental factors is most likely the cause of Type 2 diabetes. Results from twin data, familial clustering of the disease and difference in incidence according to ethnicity infer the presence of disease genes. Moreover, the sibling risk ratio, (λs; the risk of a sibling developing disease compared with general populations risk) for T2DM is up to ~18.Single nucleotide polymorphisms(SNPs),as the latest genetic markers,have great effects on the susceptibility to some chronic diseases,So it is significant to search relative SNPs from FDR(first degree relatives of T2DM patient) genes.Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet induced obesity, as well as increased sensitivity to insulin and to leptin. As we know,IR(insulin resistance) is one of the most important pathogenetic factors for T2DM,and obesity is the number one risk factor for type 2 diabetes.So,We suggested DGAT1 may be a candidate gene for T2DM. Template-directed dye-terminator incorporation with fluorescence polarization detection(TDI-FP)is a sensitive and specific method to detect SNPs.It was used in our study to detect DGAT1 Lys-378Asn(K378N) polymorphisms.MethodsThe present study included 41 T2DM pedigrees, recruited from inpatients of endocrinology department of Tangdu Hospital of the 4th Military Medical University from 2004 to 2007. 134 patients diagnosed by WHO (1999) criteria were divided into three subgroups:①The T2DM group(n=76,35 males and 41 females), all of them presented type 2 diabetes cases in two consecutive generations and whose number of sib relatives suffered T2DM≥2;②The NDR group(n=59,21 males and 38 females) ,the first-degree-relatives of the T2DM group without T2DM;③The NC group (n=45,21 males and 24 females) , no kinship with the T2DM group and without T2DM or IGR excluded by OGTT.We dectectd the polymorphism of DGAT1 with TDI-FP and compared the gene frequency and allelic gene frequency in each group. Moreover,the study invoved clinical assessments and laboratory investigations of all of the participants.Results1. The distribution of DGAT1 K378N genetype in T2DM group was KK (n=59), KN (n=15) and NN(n=2); In the NDR group,it was KK (n=42), KN (n=15) and NN(n=2);In the NC group, it was KK (n=13), KN (n=23) and NN(n=9);⑴There was significant difference of the gene frequency and allelic gene frequency among the T2DM group,NDR group,and the NC group(P<0.05);But there was no significant difference of the gene frequency or allelic gene frequency between the T2DM group and the NDR group(P> 0.05).⑵By binary logistic regression,SBp and TG were the risk factors of T2DM.Compared with SBp and TG,it suggested DGAT1 may be a minor gene for T2DM.⑶There was no significant difference of the serum triglyceride(TG) levels in each group's different genotypes(P>0.05).2. In the 41 T2DM pedigrees,there were 76 subjects with T2DM,40 subjects with IGR and 19 subjects with normal glucose tolerance.By multiple regression,it is showed that SBp,TG and WHR were the risk factors for T2DM for the first-degree-relatives of T2DM patients.Conclusion1.DGAT1 K378 may be associated with the onset of T2DM,and it is may be a minor gene;but the serum TG level may be not related to DGAT1 K378N genotypes.2.By multiple regression,it is showed that SBp,TG and WHR are the risk factors for T2DM for the first-degree-relatives of T2DM patients.The results suggest that we should do effort to keep normal SBp,TG and WHR in order to prevent T2DM.