What is the impact of PCSK9 rs505151 and rs11591147 polymorphisms on serum lipids level and cardiovascular risk: a meta-analysis

Abstract

Background PCSK9 rs505151 and rs11591147 polymorphisms are identified as gain- and loss-of-function mutations, respectively. The effects of these polymorphisms on serum lipid levels and cardiovascular risk remain to be elucidated.MethodsIn this meta-analysis, we explored the association of PCSK9 rs505151 and rs11591147 polymorphisms with serum lipid levels and cardiovascular risk by calculating the standardized mean difference (SMD) and odds ratios (OR) with 95% confidence intervals (CI).ResultsPooled results analyzed under a dominant genetic model indicated that the PCSK9 rs505151 G allele was related to higher levels of triglycerides (SMD: 0.14, 95% CI: 0.02 to 0.26, P = 0.021, I2 = 0) and low-density lipoproteins cholesterol (LDL-C) (SMD: 0.17, 95% CI: 0.00 to 0.35, P = 0.046, I2 = 75.9%) and increased cardiovascular risk (OR: 1.50, 95% CI: 1.19 to 1.89, P = 0.0006, I2 = 48%). The rs11591147 T allele was significantly associated with lower levels of total cholesterol (TC) and LDL-C (TC, SMD: -0.45, 95% CI: -0.57 to −0.32, P = 0.000, I2 = 0; LDL-C, SMD: -0.44, 95% CI: -0.55 to −0.33, P = 0.000, I2 = 0) and decreased cardiovascular risk (OR: 0.77, 95% CI: 0.60 to 0.98, P = 0.031, I2 = 59.9) in Caucasians.ConclusionsThis study indicates that the variant G allele of PCSK9 rs505151 confers increased triglyceride (TG) and LDL-C levels, as well as increased cardiovascular risk. Conversely, the variant T allele of rs11591147 protects carriers from cardiovascular disease susceptibility and lower TC and LDL-C levels in Caucasians. These findings provide useful information for researchers interested in the fields of PCSK9 genetics and cardiovascular risk prediction not only for designing future studies, but also for clinical and public health applications.

Characterization of LDLR rs5925 and PCSK9 rs505151 genetic variants frequencies in healthy subjects from northern Chile: Influence on plasma lipid levels

“…17 This PCSK9 genetic variant was recently associated with higher triglycerides (TG) and LDL-C levels as well as cardiovascular risk; associated with severity of coronary atherosclerosis in Caucasian, African-Americans, and American Indian; and also associated with hypercholesterolemia in men but not in women in European population. [17][18][19][20][21] Previously reported, PCSK9 rs505151 genetic variant was associated with higher LDL-C levels and affected lipid-lowering response to atorvastatin in individuals from the south of Chile. 22,23 On the other hand, no association was found between PCSK9 rs505151 genetic variant and LDL-C in old individuals with vascular disease from Scotland, Ireland, and the Netherlands, and young and middle age African-American and non-Hispanic black population.…”

Serum PCSK9 levels, but not PCSK9 polymorphisms, are associated with CAD risk and lipid profiles in southern Chinese Han population

“…However, the results were inconsistent. In 2015 and 2017, three meta-analyses were carried out to clarify the association between PCSK9 E670G polymorphism and lipid levels and the risk of CAD [7][8][9]. Although pooled effects indicated that G allele carriers had a higher risk of CAD and LDL-C levels than non-carriers, the heterogeneity among the studies was statistically significant, suggested that the results should be interpreted cautiously.…”

“…Data from previous studies indicated that the variant of R46L is rare in both Caucasians and Asians [10,11]. Caucasians carriers of the minor allele had lower cardiovascular disease susceptibility and lower LDL-C levels [9]. However, no study has been conducted on the relationship between the PCSK9 R46L polymorphism and lipid levels and cardiovascular risk in a Chinese population.…”

Hypolipidaemia among patients with PMM2-CDG is associated with low circulating PCSK9 levels: a case report followed by observational and experimental studies

“…The proband was heterozygous for one known LOF PCSK9 variant (p.10Leu insertion), whereas the father was heterozygous for two LOF PCSK9 variants (p.10Leu insertion and p.Arg46Leu). Other studies have demonstrated that heterozygosity for the p.Arg46Leu and p.10Leu insertion variants is associated with a 15%, and 14.2% reduction in LDLc, respectively 21–23. Based on the aggregate genetic effect of LOF PCSK9 variants, the father was predicted to have had 29.2% lower LDLc (11th percentile), and the proband was predicted to have had 14.2% lower LDLc (28th percentile).…”