Haplotype Analysis of Peroxisome Proliferator-activated Recep-tor γ Gene Polymorphisms and the Lipoprotein (a) Level

Background: Lipoprotein (a) [Lp(a)], as an independent risk factor for cardiovascular disease, is more likely to be genetically determined according to the increasing evidence of epidemiologic and clinical studies in recent years. Peroxisome proliferator-activated receptor (PPAR) γ, the ligand-activated transcription factors, was considered as an indispensable role in the process of lipid metabolism. This study was designed to explore the associations of three single-nucleotide polymorphisms (SNPs) and the haplotypes of the peroxisome proliferator-activated receptor (PPAR)γ gene with the level of Lp(a). Methods: Participants were recruited under the framework of the PMMJS (The Prevention of Metabolic Syndrome (MS) and Multi-metabolic Disorders in Jiangsu Province of China Study) from Apr 1999 to Jun 2004. Overall, 644 subjects were randomly selected and 3 SNPs of PPARγ gene (rs10865710, rs1805192, rs4684847) were genotyped. Results: After adjusting for age, sex, cigarette smoking, alcohol drinking, waist circumference and body mass index, rs4684847 was significantly associated with Lp (a). The presence of the rs4684847 T allele (CT+TT) have a lower level of Lp (a) than the allele (CC) in the dominant model, mean difference was -27.30 (95% CI: -52.88∼-1.73) mg/L, P<0.05. G-P-T and G-A-T haplotype were associated with lower levels of Lp (a) (P=0.0041 and <0.0001), mean difference was 49.79 (95% CI: -97.52∼-2.06) mg/L and 17.75 (95% CI: -25.75∼-9.75) mg/L. Conclusion: PPAR gamma polymorphisms (rs10865710, rs1805192, rs4684847) and haplotypes may be the genetic risk factors for Lp (a) level.