Studies On Genetic Association Between Lipoprotein Lipase Gene Polymorphisms And Type 2 Diabetes In Chinese Han Population Of Hubei

Objective: Type 2 diabetes mellitus (T2DM) is complex disease characterized by elevated blood glucose level that results from insulin resistance and deficiency inβcell secretion.Genetic factor plays a significant role in the development of T2DM. It has been showed that elevated plasma triacylglycerol and fatty acid are usually related to elevated insulin resistance, suggesting that genes in the pathway of lipid metabolism might be involved in the development of T2DM. With the development of pathophysiology and molecular biology, numerous candidate genes in the lipid metabolism had been identified.The lipoprotein lipase (LPL), a key enzyme in the lipid metabolism, catalyses the hydrolyzation of plasma triacylglycerol and helps the maturity of high density lipoprotein and low density lipoprotein.Methods: The association of a HindIII RFLP (restriction fragment length polymorphism) and a Pvu II RFLP in the LPL gene with T2DM in Han Chinese in Hubei province was investigated using X~2 test and logistic regression analysis. Genotypes were determined by PCR-RFLP in 102 controls and 264 T2DM patients using sib-pair and unrelated case-control designs.Results: (1) There were significant differences in the genotypic and allelic frequencies of the Hindlll polymorphism between cases and controls in all subjects studied as well as between sibpair cases and controls. Logistic regression analysis indicated that the Hindlll polymorphism was significantly associated with T2DM in all subjects. Multivariate logistic regression analysis indicated that fasting plasma glucose and Hindlll polymorphism were independent risk factors of T2DM. ANOVA showed that the Hindlll polymorphism was not related to the clinical phenotype in both cases and controls.(2) No differences in the genotypic and allelic frequencies of the Pvu II polymorphism in the LPL gene were observed between cases and controls in both of study designs. Logistic regression analysis indicated that the Pvu II polymorphism was not significantly related to T2DM in all subjects. After adjusting sex, age, hypertension and obesity, result remained unsignificant. ANOVA showed that there were significant differences in waist circumference and hip circumference among three genotypes of the Pvu II polymorphism in cases group, while there were significant differences in SBP and DBP among three genotypes of the Pvu II polymorphism in controls group.(3) Haplotype analysis indicated that there were significant differences in the haplotype frequencies of the LPL gene between sibpair cases and controls. The haplotype H+P+ was associated with higher risk of T2DM.Conclusions: The LPL gene is associated with T2DM and is a susceptibility gene for T2DM in Han Chinese in Hubei province.