Genetic variation in members of the leukotrienes biosynthesis pathway confers risk of ischemic stroke in Eastern Han Chinese.
This study was aimed to explore the association of genetic variation in members of the leukotrienes biosynthesis pathway as potential mediators with ischemic stroke (IS) risk in Eastern Han Chinese. A case-control study of was conducted with five selected single nucleotide polymorphisms (SNPs). In the single-locus analysis, carriers of C allele of rs730012 in LTC4S were more susceptible to IS (OR, 1.28; 95% CI, 1.02-1.60; P=0.033). Under the recessive genetic model, ALOX5 rs2029253 variant reduced IS risk (adjusted OR, 0.78; 95% CI, 0.60-1.00; P=0.048) while LTA4H rs6538697 and LTC4S rs730012 variants increased (adjusted OR, 1.66; 95% CI, 1.04-2.64; P=0.032 and adjusted OR, 3.63; 95% CI, 1.01-13.05; P=0.048, respectively). However, there was no evidence of association between all five SNPs and IS risk after correction for multiple testing. In combined analysis of multiple genes and loci, individuals with ALOX5AP rs12429692 T allele, ALOX5 rs2029253 A allele, and LTA4H rs6538697 C allele suggested a significantly increased susceptibility to IS (adjusted OR, 1.70; 95% CI, 1.07-2.69; P=0.024). The present study suggested gene-gene interactions in leukotrienes pathway could exert influences on the risk of IS.
Emergency center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China. wgn20050819@126.com
Gannan
G
Wang
Jinsong
J
Zhang
Hao
H
Sun
Weijuan
W
Cao
Jing
J
Zhang
Yao
Y
Wang
Hang
H
Xiao
D000368:Aged; D000483:Alleles; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005808:Genes, Recessive; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020521:Stroke / Q000235:genetics* / Q000378:metabolism
D015289:Leukotrienes; D001094:Arachidonate 5-Lipoxygenase; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C041116:leukotriene-C4 synthase; C043134:leukotriene A4 hydrolase