Lipoprotein lipase gene mutations and the genetic susceptibility of preeclampsia

In the pathogenesis of preeclampsia, endothelial cell activation or dysfunc tion is a central theme, and marked dyslipidemia may contribute to endothel ial cell dysfunction. The objective of this study was to evaluate the assoc iation between preeclampsia and mutations within the lipoprotein lipase (LP L) gene. DNA was extracted from whole blood or cheek swabs of 250 preeclamp tic patients, 265 control subjects, and 106 offspring of preeclamptic patie nts (all white). Control subjects were women who had undergone greater than or equal to2 term pregnancies unaffected by preeclampsia. All samples were genotyped for 3 LPL polymorphisms with the use of polymerase chain reactio n of known allelic variants. The 3 mutations studied were the following: (1 ) Asp9Asn substitution in exon 2, (2) T-to-G substitution at position -93 o f the proximal promotor region (-93T/G), and (3) Asn291Ser substitution in exon 6. Results were analyzed with an chi (2) contingency table. The preval ences of the Asp9Asn mutation, -93T/G promotor mutation, and Asn291Ser muta tion were not significantly different among the preeclamptic patients and c ontrol subjects (Asp9Asn: patients, 2.8%; control subjects, 4.0%, -93T/G: p atients, 4.5%; control subjects, 5.5%; Asn291Ser: patients, 4.0%; control s ubject, 3.0%). In addition, there was no difference in the frequency of any of the mutations in the offspring of preeclamptic women compared with that observed in the control population. Between a small group of patients with nulliparous HELLP syndrome (a variant of severe preeclampsia: hemolysis, e levated liver enzyme, low platelets) patients (n=12) and control subjects, there was a significant difference in the prevalence of the Asn291Ser mutat ion (16.7% versus 3.0%, P = 0.01). In this large white population, the Asp9 Asn mutation. - 93T/G promotor mutation, and Asn291Ser mutation were not as sociated with an increased risk for preeclampsia. In a small subgroup of pa tients, the Asn291Ser mutation was associated with an increased risk for nu lliparous HELLP syndrome.