Variants in the lipoprotein lipase gene and paraoxonase gene and risk of preeclampsia

Endothelial dysfunction is a central component in the pathogenesis of preeclampsia, a vascular disorder during pregnancy. Hypertriglyceridemia plays an important role as a promoter of lipid peroxidation-induced endothelial dysfunction, and thus contributes to the development of preeclampsia. Lipoprotein lipase (LPL) is a rate-limiting enzyme that regulates the clearance of circulating triglycerides and the metabolism of lipoproteins. Paraoxonase (PON1) is a high-density lipoprotein-bound enzyme that can prevent oxidation of low-density lipoproteins and thus exerts an anti-atherogenic effect. Variants of the LPL gene (i.e. N291S, S447X and D9N) and the PON1 gene (i.e. Q192R, L55M and C(−108)T) have been related to coronary heart disease and atherosclerosis risk in multiple studies of men and non-pregnant women. Results from two studies of pregnant women concerning the relationship between LPL variants and preeclampsia risk were inconsistent. We are not aware of published reports concerning preeclampsia risk and PON1 polymorphism. In a case-control study of 144 preeclampsia cases and 290 normotensive pregnant women (all non-Hispanic Caucasians), we studied variants of the LPL gene and PON1 gene in relation to preeclampsia risk. In addition, we explored the extent to which, if at all, these associations were modified by non-genetic factors. Single nucleotide polymorphisms were determined using TaqMan™ based allelic discrimination assays. We estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for maternal age, pre-pregnancy body mass index and parity. The genotype frequency of each variant in the LPL gene or PON1 gene was in Hardy-Weinberg equilibrium among controls. The LPL 291S variant allele was more frequent in cases than controls (3.1% vs. 0.9%). Women with the N/S or S/S genotype experienced more than a 6-fold increased risk of preeclampsia (adjusted OR = 6.9, 95% CI 1.9–25.4) compared with women with N/N genotype for the N291S variant. We, however, found no evidence suggestive of an association between preeclampsia risk and the LPL S447X variant, any of the PON1 genotypes or haplotypes. Notably, positive associations of preeclampsia risk with LPL S447X and PON1 L55M were observed among sub-groups of study subjects defined by non-genetic factors. Future studies are warranted to confirm and extend these findings.