Background: Studies on the associations of the adenosine triphosphate-binding cassette transporter A1 gene (ABCA1) rs2230806, rs2230808, and rs2066714 polymorphisms with plasma lipid levels have reported apparently conflicting findings. This meta-analysis aimed to clarify the relationships between the 3 polymorphisms and fasting lipid levels. Methods: A comprehensive search of the literature was carried out by using the databases including Medline, Google Scholar, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and VIP. The studies that presented mean lipids and standard deviations or standard errors according to the rs2230806, rs2230808, and/or rs2066714 genotypes were examined and included. The random effects model was used. Standardized mean difference and 95% confidence interval were used to assess the differences in lipid levels between the genotypes. Heterogeneity among studies was tested by Cochran's χ²-based Q-statistic, and Galbraith plots were used to detect the potential sources of heterogeneity. Publication bias was assessed by Begg's rank correlation test as well as funnel plots. Results: Sixty-two studies (48,452 subjects), 12 studies (9853 subjects) and 14 studies (10,727 subjects) were identified for the rs2230806, rs2230808, and rs2066714 polymorphisms, respectively. A dominant model was used for all the polymorphisms in this meta-analysis. The A allele carriers of the rs2230806 polymorphism had higher levels of high-density lipoprotein cholesterol (HDL-C) (P <.001), and lower levels of low-density lipoprotein cholesterol (LDL-C) (P =.03) and triglycerides (TG) (P <.01) than the non-carriers. The A allele carriers of the rs2230808 polymorphism had higher levels of total cholesterol (TC) (P <.001) than the non-carriers. The G allele carriers of the rs2066714 polymorphism had higher levels of TC (P <.01) and HDL-C (P = .02) than the non-carriers. Conclusion: The ABCA1 rs2230806, rs2230808, and rs2066714 polymorphisms are significantly associated with plasma lipid levels in the present meta-analysis.

Background. Adiponectin is a recognized antiatherogenic molecule; this study was aimed at clarifying the effects of adiponectin variants on lipid and adiponectin levels. Methods. By searching PubMed and Cochrane databases for studies published before March 31, 2022, a total of 86,610 individuals were included in the analysis. Results. Variants of rs2241766 and rs266729 were associated with decreased adiponectin and high-density lipoprotein cholesterol (HDL-C), as well as increased triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the rs1501299 variant was correlated with increased adiponectin and HDL-C, as well as decreased TG, TC, and LDL-C levels. Subgroup analysis indicated that the significant effect of the rs2241766 and rs266729 variants on lipid profile was predominant in Chinese, while the significant effect of the rs1501299 variant on lipid profile was primarily in Caucasians. Moreover, a stronger effect of the rs2241766 and rs1501299 variants on LDL-C levels was observed in males, while a considerable effect of the rs266729 variant on LDL-C levels was observed in children. Conclusions. The present study indicated that Chinese with the rs2241766 and rs266729 variants were at high risk of dyslipidemia, atherosclerosis, or coronary artery disease (CAD). Males with the rs2241766 variant were at high risk of CAD. Children with the rs266729 variant had a high risk to develop dyslipidemia, atherosclerosis, and even early onset of CAD in the future. These findings are beneficial to clinical physicians to choose different management strategies for cardiovascular disease (CVD) prevention.

Background: The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency. Methods: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023. Results: Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals. Conclusions: The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.

Background: Several 9p21.3 variants, such as rs1333049, rs4977574, rs10757274, rs10757278, and rs10811661, identified from recent genome-wide association studies (GWASs) are reported to be associated with coronary artery disease (CAD) susceptibility but independent of dyslipidemia. This study investigated whether these 9p21.3 variants influenced lipid profiles.Methods and results: By searching the PubMed and Cochrane databases, 101,099 individuals were included in the analysis. The consistent finding for the rs1333049 C allele on lipid profiles increased the triglyceride (TG) levels. Moreover, the rs4977574 G allele and the rs10757274 G allele, respectively, increased low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels. However, the rs10811661 C allele largely reduced LDL-C levels. Subgroup analyses indicated that the effects of the rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele on lipid profiles were stronger in Whites compared with Asians. In contrast, the effect of the rs10811661 C allele on lipid profiles was stronger in Asians compared with Whites.Conclusion: The rs1333049 C allele, rs4977574 G allele, and rs10757274 G allele of lncRNA, and the rs10811661 G allele of CDKN2A/2B had a significant influence on lipid levels, which may help the understanding of the underlying mechanisms between 9p21.3 variants and CAD.

Background: Cytokine storm is known to impact the prognosis of coronavirus disease 2019 (COVID-19), since pro-inflammatory cytokine variants are associated with cytokine storm. It is tempting to speculate that pro-inflammatory cytokines variants may impact COVID-19 outcomes by modulating cytokine storm. Here, we verified this hypothesis via a comprehensive analysis. Methods: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 15, 2023. Case–control or cohort studies that investigated the impacts of rs1800795 or rs1800629 on COVID-19 susceptibility, severity, mortality, IL-6, TNF-α, or CRP levels were included after an anonymous review by two independent reviewers and consultations of disagreement by a third independent reviewer. Results: 47 studies (8305 COVID-19 individuals and 17,846 non-COVID-19 individuals) were analyzed. The rs1800629 A allele (adenine at the −308 position of the promoter was encoded by the A allele) was associated with higher levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). In contrast, the rs1800795 C allele (cytosine at the −174 position of the promoter was encoded by the C allele) was linked to higher levels of interleukin-6 (IL-6) and CRP. In addition, the A allele of rs1800629 increased the severity and mortality of COVID-19. However, the C allele of rs1800795 only increased COVID-19 susceptibility. Conclusions: rs1800629 and rs1800795 variants of pro-inflammatory cytokines have significant impacts on systemic inflammatory profile and COVID-19 clinical outcomes. rs1800629 may serve as a genetic marker for severe COVID-19.

Our previous study reckons that the impact of the rs1801133 variant of 5,10‐methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD‐free individuals were enrolled in this case–control study. The rs1801133 variant was genotyped by PCR‐RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD‐free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low‐density lipoprotein cholesterol (LDL‐C), and high‐sensitivity C‐reactive protein (hs‐CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision‐recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs‐CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.