Nonsynonymous polymorphisms in PLA2G7 gene are associated with the risk of coronary heart disease in a southern Chinese population

Abstract

Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays an important role in coronary heart disease (CHD). This study was aimed to investigate the associations of polymorphisms (R92H, V279F, I198T, and A379V) in PLA2G7 with CHD. A total of 322 patients with CHD and 414 CHD-free controls were included in the study. Polymorphisms in PLA2G7 were sequenced by DNA Sequencer and statistical analyses were performed to study the associations between polymorphisms and CHD. 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). Correlations between R92H and CHD still existed after adjustment for confounding risk factors of CHD (P = 0.001). Furthermore, stratified analyses showed subgroups of the senior, hypertension, non-smoking, non-diabetics, and male subjects brought a higher risk for CHD (P = 0.015, P = 0.001, P = 0.001, P = 0.002, and P = 0.004, respectively). We also observed a lower level of protective factor HDL-C in CHD patients carrying genotype RH + HH than patients with RR (P = 0.047). Furthermore, we conducted haplotype analysis and detected more harmful effects of haplotypes HVI and RVT as compared with other haplotypes (P = 2.538 × 10(-3) and P = 0.031). These findings indicated that R92H variant in PLA2G7 gene might contribute to CHD susceptibility in a southern Chinese population.

Lipoprotein‐associated phospholipase A2: The story continues

“…Similar to other polymorphisms in PLA2G7 , the results of the correlation research on this allele in vascular disease are still complicated. Hong et al found that the T198 allele would not affect the risk of CHD in a Chinese population (OR = 1.26, 95% CI: 0.85‐1.87). Likewise, Ferguson et al failed to uncover a significant association between the I198T polymorphism and coronary artery calcification (CAC).…”

“…Similar to other polymorphisms in PLA2G7, the results of the correlation research on this allele in vascular disease are still complicated. Hong et al 103 CHD (OR = 1.51, 95% CI: 1.23-1.97). Although these studies were carried out in different populations, the clearly opposing results highlight the need for further investigations to elucidate whether this genetic variant is associated with the risk and outcome of CVD.…”

“…For vascular diseases, the effect of the R92H variant was inconsistent in different studies. Along the lines of the results summarized by Stafforini in the European population, the H92 variant was associated with an increased risk of vascular diseases in the Chinese population by Zheng et al (OR = 1.81, 95% CI: 1.18‐2.78), Xu et al (OR = 1.63, 95% CI: 1.02‐2.62), Ma (OR = 1.42, 95% CI: 1.02‐2.00), Hong et al (OR = 2.66, 95% CI: 1.50‐4.69), and Chi et al (OR = 1.45, 95% CI: 1.16‐1.92). Additionally, a recent meta‐analysis also yielded a significantly positive association between R92H mutation and clinical atherosclerosis (OR = 1.29, 95% CI: 1.09‐1.53) .…”

Cross-Species Analysis of Gene Expression and Function in Prefrontal Cortex, Hippocampus and Striatum

“…Abnormally expressed PLA2G7 may give rise to dysregulation of phospholipid metabolism. PLA2G7 gene has been widely studied as a candidate risk factor of coronary heart disease [ 67 , 68 ]. Only a few reports endeavored to explore the potential roles of PLA2G7 in neurophysiological processes and pathological disorders.…”

<p>Human Secretary Phospholipase A2 Mutations and Their Clinical Implications</p>

“…[51][52][53][54][55][56][57] Few other studies show V279F, R92H, A379V, D166E to be having a frank cardiovascular disease (CVD) risk. 54,[58][59][60][61][62][63][64][65]…”