Associations Of Two Inflammation Genes-PLA2G7 And TNF With Coronary Heart Disease In A Chinese Han Population

Section one:PLA2G7The human PLA2G7 gene encodes lipoprotein-associated phospholipase A2(Lp-PLA₂), an emerging risk factor for cardiovascular diseases.In the present study,eight single nucleotide polymorphisms(SNPs) in the PLA2G7 gene were genotyped in 827 patients with coronary heart disease(CHD),of which 512 were patients with myocardial infarction(MI),and 947 age- and gender-matched controls in a Chinese Han population. Plasma Lp-PLA₂ activity was measured in 416 randomly selected controls and 689 randomly selected CHD patients,including 423 MI patients.Lp-PLA₂ activity in CHD and MI cases was significantly higher(233.42±57.66 and 234.27±59.51 nmol/ml/min,respectively) than in controls(211.47±58.61 nmol/ml/min).After adjusting for traditional risk factors by logistic regression,the odds ratios for CHD and MI per 1 standard deviation increment of Lp-PLA₂ activity were 1.27(95%CI,1.07-1.50) and 1.27(95%CI, 1.05-1.54),respectively.Both single SNP analysis and haplotype analysis showed that the V279F and I198T polymorphisms were significantly associated with the reduced Lp-PLA₂ activity but neither was associated with increased CHD risk.Both univariate and multivariate analyses,adjusting effects of conventional factors,indicated that the rs13210554 T allele increased the risk of MI in this Chinese Hart population.In summary,an independent association of increased plasma Lp-PLA₂ activity with CHD and MI existed in this Chinese Han Population.Although V279F and I198T mutations significantly decreased the activity of Lp-PLA₂,only the promoter rs13210554 polymorphism was associated with MI. Lp-PLA₂ activity appears to influence the CHD and MI risk in Chinese Han population.Section two:TNFTumor necrosis factor alpha(TNF-α) is a primary pro-inflammatory cytokines and has been implicated in cardiovascular disease pathogenesis.Relationship between polymorphisms in TNF gene and CHD has been reported,but remains a controversial one.A single nucleotide polymorphism(SNP) discovery in a total of 4739 base pairs in the promoter region,exon region and exon/intron boarding region of TNF gene in randomly selected 48 patients by direct sequencing was conducted.Four SNPs(-806C＞T,-308G＞A, -238G＞A,and +467G＞A) out of seven polymorphisms identified were further investigated for associations in 804 CHD patients(of which 504 patients with MI) and 905 age-and gender-matched controls.No main effects of loci and haplotypes reached statistical significance in the total sample.However,a significant gene-smoking interaction was observed. In nonsmokers,compared with individuals of G/G genotype,individuals carrying the A allele of the -238G＞A polymorphism showed a lower risk of developing CHD(odds ratio 0.48,95%CI 0.24-0.94,P=0.033),and an even lower risk of developing MI(odds ratio 0.36,95%CI 0.15-0.88,P=0.026).Haplotype analysis confirmed the results of individual polymorphism analyses.In addition,the -806C＞T polymorphism was found to be associated with MI in smokers(P=0.039).This study identified a significant interaction between TNF gene and smoking status.Both single locus and haplotype analyses indicated that A allele of the -238G＞A polymorphism decreased the risk of CHD among nonsmokers in Chinese Han population.