Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and risk of ischemic stroke in Han Chinese of eastern China

Abstract

Variants of the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene have been suggested to play an important role in the pathogenesis of atherosclerosis and ischemic stroke. This study was aimed to explore the association of ALOX5AP variants with ischemic stroke risk in Han Chinese of eastern China. A total of 690 ischemic stroke cases and 767 controls were recruited. The subjects were further subtyped according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of that, two polymorphisms of the ALOX5AP gene (rs10507391 and rs12429692) were determined by TaqMan genotyping assay. In addition, plasma leukotriene B4 (LTB4) levels were analyzed in these subjects. There was no evidence of association between the two variants of ALOX5AP and the risk of ischemic stroke or its TOAST-subtypes. Haplotype analysis and stratification analysis according to sex, age, body mass index, hypertension, and diabetes also showed negative association. Analysis of LTB4 levels in a subset of cases and controls revealed that LTB4 levels were significantly higher in ischemic stroke cases than in the controls (70.06±14.75 ng/L vs 57.34±10.93 ng/L; P = 0.000) and carriers of the T allele of the rs10507391 variant were associated with higher plasma LTB4 levels (P = 0.000). The present study suggests there is no association of the two polymorphisms in the ALOX5AP gene with ischemic stroke risk in Han Chinese of eastern China.

<p>Lack of association between <em>ALOX5AP</em> genetic polymorphisms and risk of ischemic stroke: evidence from meta-analyses</p>

“…First, the relationship between the ALOX5AP polymorphisms and the levels of leukotriene lipid mediators in IS patients was not evaluated due to lack of published data. Increased levels of products of the 5-lipoxygenase (5-LO)/5-LO-activating protein (FLAP) pathway including LTB4 had been reported in IS patients 45. The evaluation of potential interactions between ALOX5AP polymorphisms and leukotriene lipid mediators in IS patients could provide valuable insights into the development of IS.…”

Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians

“…None of the SNPs in either group showed significant association with the disease. The genetic contribution of Hap A and Hap B and their individual SNPs to the cardiovascular phenotypes in Whites, Blacks, and East Asian populations have yielded both positive [11,12], and negative results [17][18][19]33]. In the Icelandic population, Hap A showed association with MI, with a case/control frequency of 0.158/0.095 [12], but no association in the Scottish (0.184/0.142) [11] and Caucasian (0.15/0.15) [34] populations.…”

Association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China

“…The results might be due to the etiology of IS, which is infl uenced by multiple genes, and each single susceptibility gene may exert marginal effects. [27] Since IS is a complex disease involving multiple genetic variations and gene-environment interactions, a single locus cannot fully explain their genetic susceptibility. [28] Therefore, analysis of the combined effects of multiple genes and multi-locus could capture more information about IS risk than analysis of a single susceptibility gene or locus.…”