• Zhi G Su, Si Z Zhang, Yi P Hou, T Li, Daniel W Nebert, L Zhang, De J Huang, Lin C Liao, and Cui Y Xiao.
• Department of Medical Genetics, West China Hospital, Sichuan University, Sichuan, Chengdu 610041, China.
• Eur. J. Pharmacol. 2002 Nov 1; 454 (1): 9-18.

AbstractCoronary heart disease is a complex disease reflecting the interaction of multiple genes with the environment (e.g. diet, life style). Lipoprotein lipase (LPL) plays an important role in lipid metabolism and the pathogenesis of coronary atherosclerosis. Recent associations between single-nucleotide polymorphisms in the LPL gene and heart disease have been reported, but little is known in Chinese. The LPL gene spans >26 kb, with an mRNA of 3549 bp. In the present study, we screened 5155 bp (565 bp of 5' flanking region, nine exons and donor- and acceptor-splice sites, and some intronic bases) in 160 Chinese patients with confirmed coronary heart disease and 150 age- and gender-matched controls. Thirteen of the sixteen single-nucleotide polymorphisms that we found have not been previously reported. In males, significant (P<0.05) differences between the coronary heart disease patients and controls were found for five single-nucleotide polymorphisms: -421G>A (5' flanking region); +13,577C>A (intron 2); +16,052G>A, R192Q (exon 5); +16,173C>G and +16,177T>C (intron 5). In females, significant differences between the patients with coronary heart disease and controls were found for only the -421G>A and +16,052G>A (R192Q) mutations. Among the coronary heart disease males, significant (P<0.05) associations were found between the low-HDL high-triglyceride (LHDL/HTG) phenotype and the non-LHDL/HTG trait for the 5' flanking-421G, the intron 2+13,577C, and the exon 5+16,052G mutations, with odds-ratios (ORs)[confidence intervals] of 3.90[1.12-13.66], 3.38[1.22-9.40], and 3.22[1.04-10.01], respectively; no corresponding associations were found in females. There were 69, 51, 57 and 41 unphased haplotype patterns in male coronary heart disease, male control, female coronary heart disease and female control groups, respectively; the computer program PM-Plus found the heterogeneity model by far the best fit (P<0.0001 in males, >0.01 in females). These data show that some single-nucleotide polymorphisms in the LPL gene among Chinese are associated with abnormal lipid and lipoprotein profiles and predisposition to coronary heart disease, a genetically heterogeneous complex disease, and that they are gender-specific.

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