| Objective Up to now the prevalence rate of diabetes mellitus (DM)is more than 3.6 % in the mainland of China, and it has been anticipated that the number of DM patients ,in which diabetic nephropathy (DN) patients account for 19%, will come to 60 million in 2010. It is suggested that type 2 diabetes mellitus(T2DM) and its microvascular complication—DN have heredity susceptibility in genealogy researches and racial prevalence surveys. Singlenucleotide polymorphisms (SNPs), as the new genetic markers, may have great effects on the susceptibility to some chronic diseases such as DM and coronary heart disease etc. So it will be significant to search genes SNPs which may predict the susceptibility or prognosis of DM and DN in order to block or reverse their pathogenetic processes earlier.Diacylglycerol acyltransferase (DGAT) enzyme catalyzes the final step in mammalian triglyceride(TG) synthesis. DGAT1-def icient mice are resistant to diet induced obesity and have increased insulin and leptin sensitivity. So DGAT1 is suggested to be associated with IR and obesity. As we know IR is one of the most important pathogenetic factor of T2DM, and obesity is a risk factor of T2DM. It has been reported that DGAT1 gene polymorphism was related to low body mass index(BMI), DGAT1 gene may be a candidate gene for T2DM or DN.Paraoxonase2(PON2) gene is related with lipid metabolism, the product of which can reduce the level of oxidized low density lipoprotein (ox—LDL) and has antioxidant properties. Oxidative stress may play an important role in the onset and development of DM and DN. PON2 gene is close to DNA maker for insulin resistance(IR) and T2DM in Pima Indians, and PON2 Ser311Cys (S311C) gene polymorphism has been reported to be related to coronary heart disease and diabetic microvascular complication.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 case-controlstudy to detect DGAT1 Lys378Asn (K378N) and P0N2 S311C polymorphisms in order to investigate if the two candidate SNPs were related to Chinese T2DM or DN.Methods 94 patients with T2DM( T2DM group) were recruited frominpatients of endocrinology department of Tangdu Hospital of the 4th Military Medical University from May 2003 to September 2004. There were 29 DN patients (DN +group) with 17 patients who had proteinuria and hypertention without diabetic retinopathy excluded. There were 42 patients without DN(DN — group)with 6 patients who had not proteinuria but had diabetic retinopathy excluded. 45 healthy controls were randomly selected from health examination center of Tangdu Hospital. There were no significant differences in age, sex and BMI between each group. DGAT1 K378N and P0N2 S311C polymorphisms were genotyped by TDI-FP. Then . the statistical analyses were performed for possible significant differences between the frequencies of alleles and genotypes in different groups.Results1 In the T2DM group, there were 42 carriers of DGAT1KK genotype, 40 of KN genotype and 12 of NN genotype; In the DN+ group, there were 14 carriers of DGAT1 KK genotype, 11 of KN genotype and 4 of NN genotype; In the DN- group, there were 22 carriers of DGAT1 KK genotype, 14 of KN genotype and 6 of NN genotype; In the control group, there were 13 carriers of DGAT1 KK genotype, 23 of KN genotype and 9 of NN genotype. (1) The frequency of DGAT1 K378 allele wasincreased in Patients with T2DM , but there was no significant difference in comparison with normal controls (PX). 05) . (2) There was no significant difference of DGATl K378N alleles and genotypes between DN+ and DN- groups (P>0. 05) . (3) There was not different significantly in the serum triglyceride (TG) levels of each group' s different genotypes (P>0. 05) .2 In the T2DM group, there were 35 carriers of P0N2 SS genotype, 36 of CS genotype and 23 of CC genotype; In the DN+ group, there were 11 carriers of P0N2 SS genotype, 12 of CS genotype and 6 of CC genotype; In the DN- group, there were 15 carriers of P0N2 SS genotype, 16 of CS genotype and 11 of CC genotype; In the control group, there were 23 carriers of P0N2SS genotype, 16 of CS genotype and 6 of CC genotype. (1) Patients with T2DM had a higher frequencyof P0N2 C311 allele than normal controls ( x2 =3. 981, P<0. 05,0R=1.713, 95%CI: 1.007-2.914) . (2) There was no significant difference of P0N2C311S alleles and genotypes between DN+ and DN-groups (P>0. 05) . (3) It was found by binary logistic regression with T2DM as dependent variable that systolic blood pressure (SBp) and TG entered the regression equation, P0N2 C311 allele could not enter the equation. It was suggested that P0N2 C311 allele was a minor gene of T2DM in comparison with SBp and TG. (4) There might be.no interaction between DGATl K378N and P0N2SZWC polymorphisms in T2DM and DN by dichotomy analysis.Conclusions (1) K378 allele is increased in the T2DM group but it is not remarkable statistically. DGATl K378N may not be...
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