Association between the ABCA1 (R219K) polymorphism and lipid profiles: a meta-analysis

Abstract

Conflicting evidence was found about the relationship between lipid profiles and R219K polymorphism in adenosine triphosphate-binding cassette exporter A1 (ABCA1) gene. In this study, four meta-analyses were conducted to assess the effect of R219K on lipid levels, including high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, total cholesterol, and triglycerides (TG). A total of 125 samples of 87 studies (about 60,262 subjects) were included. The effect of each study was expressed using the standard mean difference (SMD) and 95% confidence interval (95% CI) and pooled by meta-analysis in the random-effects model. Subgroup and meta-regression analyses were conducted to explore potential heterogeneity sources. The overall pooled effect showed the following results. (1) The R219K was significantly associated with HDLC level (SMD = − 0.25 mmol/L, 95%CI − 0.32 to − 0.18, z = − 6.96, P < 0.01, recessive genetic model). People with different genotypes had significantly different HDLC levels under the recessive, codominant and dominant genetic models (all Ps < 0.01). (2) A weak and indeterminate relationship between R219K and TG level was observed (SMD = 0.18 mmol/L, 95%CI 0.06–0.30, z = 3.01, P < 0.01, recessive genetic model). These findings suggested that R219K was associated with HDLC and TG levels, which might implicate a promising clinical application for lipid-related disorders, though the influences of race, health status, BMI, and other heterogeneity sources should be considered when interpreting current findings. The protocol was registered at PROSPERO (registration number: CRD42021231178).

Polymorphic Variants of AGT, ABCA1, and CYBA Genes Influence the Survival of Patients with Coronary Artery Disease: A Prospective Cohort Study

“…One such SNP is the rs2230806 polymorphism (G > A) (R219K polymorphism). The results of meta-analyses indicate that the AA genotype may be associated with higher plasma HDL cholesterol levels [ 29 , 30 ] and carrying the A allele of the rs223086 polymorphism significantly reduces the risk of CAD [ 29 , 31 , 32 ]. The A allele of the rs2230806 was also associated with a reduced risk of premature heart disease in patients with familial hypercholesterolemia [ 33 ].…”

Evaluation of ABCA1 and FNDC3B Gene Polymorphisms Associated With Pseudoexfoliation Glaucoma and Primary Angle-Closure Glaucoma in a Saudi Cohort

“…However, the exact mechanism(s) by which rs2472493 polymorphism in ABCA1 might increase PXG risk in men is unknown. The effect of gender, gene-gene, and gene-environment interactions on ABCA1 gene polymorphisms in lipid and lipoprotein metabolism have been well documented ( Junyent et al, 2010 ; Coban et al, 2014 ; Shi et al, 2021 ). The ABCA1 polymorphism might plausibly modulate the risk of PXG among men in a similar manner.…”

AI-guided screen identifies probucol-mediated mitophagy enhancement through modulation of lipid droplets

“…The K allele, which is associated with slower PD progression, also affects the lipid profile of those who carry the genotype. Compared to individuals carrying ABCA1 R219K RR or RK, ABCA1 R219K K genotype carriers have elevated high density lipoprotein cholesterol and lower triglyceride levels 51 . It remains to be determined whether the differences in lipid profiles are responsible for clinical differences between these groups.…”