Association between lipoprotein-associated phospholipase A2 gene Val279Phe homozygous genotypes and variant angina in Japanese women

Abstract Background The role of the lipoprotein-associated phospholipase A2 gene (PLA2G7) in the pathogenesis of cardiovascular diseases remains controversial. The PLA2G7 gene normally produces a protein called "plasma platelet activating factor-acetylhydrolase"(PAF-AH). Homozygotes of rs76863441, which is PLA2G7 Val279Phe polymorphism, produce none of PAF-AH, and heterozygotes produce less than half of the normal levels. This polymorphism is rare outside of Asia and is particularly common in Japan, where homozygous mutations account for 4% of the population. The association between rs76863441 and risk of myocardial infarction was significant in ethnicity for Japanese population, but not in other countries. Variant angina is a severe case of coronary artery spasm (CSA) and causes an acute myocardial infarction. It is widely accepted that variant angina is more common in Japanese than in other races. Purpose The aim of this study was to examine the possible association between rs76863441 and variant angina. Methods rs76863441 was analyzed by direct sequencing in 62 patients with variant angina (43 men and 19 women with a mean age of 60.0±11.6 years). In all patients, ST segment elevation was recorded on ECG and coronary angiography was performed. Acetylcholine provocation test was performed in 31 patients. We compared genotypes of rs76863441 between variant angina patients and 872 healthy volunteers without a history of heart diseases living in the same area, who participated in the Iwaki Health Promotion Project, which has been conducted by the Hirosaki University School of Medicine since 2005. These volunteers had undergone Japonica Arrays, which is the SNP array for the Japanese population. Results Homozygotes genotype for rs76863441, heterozygotes genotype, and wild genotype were present in 4 (6.5%), 22 (35.5%), and 36 (58.1%) of the variant angina group, respectively, and in 30 (3.4%), 246 (28.2%), and 596 (68.3%) of the control group, respectively. Statistically, there were no significant differences in genotypes between the variant angina group and the control group. Next, males and females were analyzed separately. In males, there were no significant differences in homozygous mutations (1 out of 43 patients (2.3%) in the variant angina group vs. 11 out of 327 patients (3.4%) in the control group, P=1.00). However, in females, there was a significant difference in homozygous mutations (3 out of 19 (15.8%) in the variant angina group vs. 19 out of 545 (3.4%) in the control group, P=0.033). Conclusions These findings indicate that homozygotes of rs76863441, which has PAF-AH deficiency, may be associated with the pathogenesis of variant angina in Japanese women. Further functional analyses of this mutation are of great interest.Genotypes of rs76863441Gender disparities of rs76863441