Identification of the G994--> T missense in exon 9 of the plasma platelet-activating factor acetylhydrolase gene as an independent risk factor for coronary artery disease in Japanese men.
Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.
Causal risk ratios for coronary heart disease per 65% lower Lp-PLA<sub>2</sub> activity were: 0.95 (0.88-1.03) with Val279Phe; 0.92 (0.74-1.16) with carriage of any loss-of-function variant; 1.01 (0.68-1.51) with Val379Ala; and 0.95 (0.89-1.02) with darapladib treatment.
RH + HH genotype, RH genotype, and H allele of R92H were significantly associated with an increased risk of CHD (P = 0.005, P = 0.009, and P = 0.003, respectively), while no associations were observed between V279F and I198T and CHD (A379V was not analyzed because of deviation from Hardy-Weinberg equilibrium).
The results indicate 92H allele had probably increased the risk of CHD, while the hypothesized effects of A379V and V279F polymorphisms on CHDcannot be confirmed in present data.
Both single SNP analysis and haplotype analysis showed that the V279F and I198T polymorphisms were significantly associated with the reduced Lp-PLA(2) activity, but neither was associated with increased CHD risk.
Pharmacogenetic meta-analysis of baseline risk factors, pharmacodynamic, efficacy and tolerability endpoints from two large global cardiovascular outcomes trials for darapladib.
Identification of the G994--> T missense in exon 9 of the plasma platelet-activating factor acetylhydrolase gene as an independent risk factor for coronary artery disease in Japanese men.
CHD risks were higher in carriers of homozygous mutant of rs1805017 and rs1805018 than those with wild-type homozygotes, OR (95% CI) were 1.45 (1.16-1.92) and 1.51 (1.23-1.97), respectively, but the other two SNPs, rs16874954 and rs1051931 were not significant associated with CHD risks.