Association of m.5178C>A variant with serum lipid levels: a systematic review and meta-analysis

Background: Emerging evidence shows that m.5178C>A variant is associated with a lower risk of coronary artery disease (CAD). However, the specific mechanisms remain elusive. Since dyslipidemia is one of the most critical risk factors for CAD and accounts for at least 50% of the population-attributable risk, it is tempting to speculate that the reduced CAD risk caused by the m.5178C>A variant may stem from an improved lipid profile. In order to verify this hypothesis, we conducted the present study to clarify the association of m.5178C>A variant with lipid levels.Methods: By searching ten databases for studies published before 30 June 2021. Thirteen East Asian populations (7587 individuals) were included for the analysis.Results: The present study showed that m.5178C>A variant was associated with higher high-density lipoprotein cholesterol (HDL-C) [standardized mean difference (SMD) = 0.12, 95% confidence interval (CI) = 0.06–0.17, P<0.001] and total cholesterol (TC) (SMD = 0.08, 95% CI = 0.02–0.14, P=0.01) levels. In subgroup analysis, the association of m.5178C>A variant with higher HDL-C levels were observed in Japanese (SMD = 0.09, 95% CI = 0.01–0.17, P=0.03) and Chinese populations (SMD = 0.13, 95% CI = 0.07–0.20, P<0.001). However, the association of m.5178C>A variant with lower low-density lipoprotein cholesterol (LDL-C) levels were only observed in Japanese populations (SMD = −0.11, 95% CI = −0.22 to 0.00, P=0.04).Conclusions: The m.5178C>A variant was associated with higher HDL-C and lower LDL-C levels in Japanese populations, which may contribute to decreased CAD risk and longevity of Japanese.