title: Haplotype-based association of four lymphotoxin-alpha gene polymorphisms with the risk of coronary artery disease in Han Chinese.
abstract: Lymphotoxin-alpha (LTA), a pro-inflammatory cytokine, has been implicated in the pathogenesis of coronary atherosclerosis. Meanwhile, association of some single nucleotide polymorphisms (SNPs) of LTA gene with coronary artery disease (CAD) has been evaluated; however, the results are irreproducible. We therefore investigated the relationship between four SNPs of LTA gene and CAD in Han Chinese: G+10A (rs1800683, 5'-untranslated region), A+80C (rs2239704, 5'-untranslated region), T+496C (Cys13Arg, rs2229094, exon 2), and C+804A (Thr26Asn, rs1041981, exon 3). Genotyping was performed in 438 CAD patients and 330 healthy controls. Single-locus analysis showed that the genotype and allele frequencies of G+10A polymorphism exhibited marginal differences between CAD patients and controls, although no statistical significance was observed after the Bonferroni correction. Logistic regression analysis revealed that GG genotype of G+10A polymorphism was significantly associated with the risk of CAD under the dominant mode, whereas no significant association was detected between A+80C polymorphism and CAD. In contrast, individuals carrying TT or TC genotype of T+496C polymorphism showed a decreased CAD risk relative to those with CC genotype under the recessive mode. Likewise, CC genotype of C+804A polymorphism was associated with a protective effect on CAD under the dominant mode. Further, in haplotype analysis, the haplotype G-C-T-C (in order of rs1800683, rs2239704, rs2229094 and rs1041981) was significantly associated with a decreased risk of CAD after assigning the most common haplotype A-C-T-A as a reference. In conclusion, we show a protective effect of the haplotype G-C-T-C on the occurrence of CAD, suggesting the involvement of LTA in CAD pathogenesis.
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Haihui
authors.initials: H
authors.lastname: Sheng
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wu
authors.forename: Qiujin
authors.initials: Q
authors.lastname: Chen
authors.forename: Huasheng
authors.initials: H
authors.lastname: Xiao
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
mesh_terms: D044466:Asian People / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008233:Lymphotoxin-alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D008233:Lymphotoxin-alpha