Association of PLA2G7 polymorphisms with carotid atherosclerosis in hypertensive Japanese

Abstract

Although the plasma platelet-activating factor-acetylhydrolase (pPAF-AH) gene (PLA2G7) polymorphisms are reportedly associated with atherosclerotic diseases, their effects in hypertensive patients have not been well examined. Thus, we genotyped V279F, a loss-of-function mutation commonly seen in the Japanese, and I198T and A379V commonly seen in Caucasians, and investigated the (1) ethnic differences in the frequencies and (2) association of these variants with prevalence of carotid plaque in 733 treated hypertensive Japanese patients. The distribution of V279F (V allele 75.1% and F allele 24.9%) in hypertensive patients was similar to that previously reported in the healthy Japanese; however, allele frequencies of I198T (I allele 71.7% and T allele 28.3%) and A379V (A allele 84.7% and V allele 15.3%) were markedly different from those reported in Caucasians. In addition, V279F and I198T showed a strong linkage disequilibrium (D ¢¼1.0, r 2 ¼0.89). The phenotypes showed no difference among genotypes for each polymorphism except for the blood pressure level in I198T in women. Carotid plaque was significantly more prevalent in subjects with 279F and 198T than in those with the wild type among men but not women, whereas A379V did not affect it. In multivariate logistic regression analyses, 279F and 198T were detected as an independent risk factor even after adjustments for other atherosclerotic risk factors in men. Taken together, our data suggest an ethnic difference and the possible involvement of genetic polymorphisms of PLA2G7 in the prevalence of carotid atherosclerosis in the hypertensive Japanese, especially in men.

Translational Studies of Lipoprotein-Associated Phospholipase A2 in Inflammation and Atherosclerosis

“…Including plasma Lp-PLA 2 mass or activity in the model did not attenuate the association between PLA2G7 SNPs and CAC. These findings support recent associations of variation in PLA2G7 with CHD (29–31). …”

“…However in a meta-analysis of over 13,000 Asians, a common non-synonymous PLA2G7 SNP showed evidence of association with CHD (30). Additional non-synonymous SNPs have been associated with carotid plaque in Japanese (31) and recently a loss-of-function variant in PLA2G7 was shown to protect against CHD in Koreans (29). Due to the absence in Caucasian samples of the functional PLA2G7 SNP found in Asians (rs76863441 or V279F), we were not able to evaluate the effect of this functional variant in our samples.…”

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

“…CEACAM1 [340], ACSL1 [341], TLR4 [342], ABCA1 [343], TLR5 [344], CYP2D6 [345], JAK2 [346], NOTCH2 [347], DDX3X [348], NCOA4 [349], EGR1 [350], IQGAP2 [351], GCLC (glutamate-cysteine ligase catalytic subunit) [352], VEGFA (vascular endothelial growth factor A) [353], ITGB1 [354], LDLR (low density lipoprotein receptor) [355], TLR6 [316], SIRT1 [356], FGL2 [357], TET2 [358], PHF2 [328], VEGFB (vascular endothelial growth factor B) [359], SELENOM (selenoprotein M) [360], TRPM4 [361], OLFM2 [362] and ATAD3A [363] are thought to be involved in non-alcoholic fatty liver disease. Altered expression of ATOH8 [364], STAT1 [365], ARG1 [366], TLR4 [367], VNN1 [368], ABCA1 [369], IFIH1 [370], PTGS2 [371], F2RL1 [289], CYP2D6 [372], PDK4 [373], RNF213 [374], JAK2 [375], NOTCH2 [376], PDGFC (platelet derived growth factor C) [377], TLR2 [378], CYP1B1 [379], IL1RN [380], GCH1 [381], EGR1 [382], HIF1A [383], PLA2G7 [384], CCR2 [385], GAB1 [386], VEGFA (vascular endothelial growth factor A) [387], OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [388], OXR1 [389], IRF9 [390], FMR1 [391], LDLR (low density lipoprotein receptor) [392], SIRT1 [393], NOD2 [394], ATP13A3 [395], VCAN (versican) [396], FGL2 [397], TET2 [398], KDM6A [399], KLHL2 [400], CAVIN1 [401], TNFRSF4 [402], PF4 [403], VEGFB (vascular endothelial growth factor B) [330], CCR7 [404], PRDX2 [405], HSPB1 [406], TCF4 […”

“…We used NetworkAnalyst database (https://www.networkanalyst.ca/) [45] database to find TFs regulating hub genes, IQGAP2 [351], GCLC (glutamate-cysteine ligase catalytic subunit) [352], VEGFA (vascular endothelial growth factor A) [353], ITGB1 [354], LDLR (low density lipoprotein receptor) [355], TLR6 [316], SIRT1 [356], FGL2 [357], TET2 [358], PHF2 [328], VEGFB (vascular endothelial growth factor B) [359], SELENOM (selenoprotein M) [360], TRPM4 [361], OLFM2 [362] and ATAD3A [363] are thought to be involved in non-alcoholic fatty liver disease. Altered expression of ATOH8 [364], STAT1 [365], ARG1 [366], TLR4 [367], VNN1 [368], ABCA1 [369], IFIH1 [370], PTGS2 [371], F2RL1 [289], CYP2D6 [372], PDK4 [373], RNF213 [374], JAK2 [375], NOTCH2 [376], PDGFC (platelet derived growth factor C) [377], TLR2 [378], CYP1B1 [379], IL1RN [380], GCH1 [381], EGR1 [382], HIF1A [383], PLA2G7 [384], CCR2 [385], GAB1 [386], VEGFA (vascular endothelial growth factor A) [387], OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) …”

Lipoprotein‐associated phospholipase A2: The story continues

“…Furthermore, Zheng et al demonstrated that the T198 allele was strongly associated with the risk of CHD with BSS (OR = 1.93, 95% CI: 1.21‐3.06) but not associated with the risk of CHD without BSS (OR = 1.47, 95% CI: 0.89‐2.44). Such a limited association was also observed in three studies included in Stafforini's review . Interestingly, two additional unrelated studies revealed quite different effects of the T198 allele on cardiovascular disease (CVD).…”