College of Life Science, Northwest University, Xi'an, 710069, China.
College of Medicine, Northwest University, Xi'an, 710069, China.
Sci Rep. 2021 Nov 5;11(1):21718. doi: 10.1038/s41598-021-00961-9.
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).
关于三磷酸腺苷结合盒转运体 A1(ABCA1)基因中的脂质谱与 R219K 多态性之间的关系,存在相互矛盾的证据。在这项研究中,进行了四项荟萃分析,以评估 R219K 对血脂水平(包括高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇、总胆固醇和甘油三酯(TG))的影响。共纳入了 87 项研究的 125 个样本(约 60262 例)。每个研究的效果均使用标准均数差(SMD)和 95%置信区间(95%CI)表示,并通过随机效应模型的荟萃分析进行汇总。进行了亚组和荟萃回归分析,以探讨潜在的异质性来源。总体汇总效应显示了以下结果。(1)R219K 与 HDLC 水平显著相关(SMD=-0.25mmol/L,95%CI-0.32 至-0.18,z=-6.96,P<0.01,隐性遗传模型)。在隐性、共显性和显性遗传模型下,具有不同基因型的个体的 HDLC 水平有显著差异(均 P<0.01)。(2)R219K 与 TG 水平之间存在较弱且不确定的关系(SMD=0.18mmol/L,95%CI0.06-0.30,z=3.01,P<0.01,隐性遗传模型)。这些发现表明,R219K 与 HDLC 和 TG 水平相关,这可能暗示着其在脂质相关疾病的临床应用具有潜力,尽管在解释当前结果时应考虑种族、健康状况、BMI 和其他异质性来源的影响。该方案已在 PROSPERO(注册号:CRD42021231178)上注册。