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.

Astaxanthin (ASX), a fat-soluble carotenoid mainly sourced from Haematococcus pluvialis, shows promise for clinical applications in chronic inflammatory diseases. This study investigates whether ASX can mitigate atherosclerosis (AS) by modulating macrophage ferroptosis and provides astaxanthin-loaded polylactic acid-glycolic acid nanoparticles (ASX-PLGA NPs) as comparison. ApoE-/- mice were fed a high-fat diet with ASX or statin intervention. Plaque area, lipid aggregation, collagen content, and ferroptosis-related indicators were assessed. Moreover, ASX-PLGA NPs were synthesized and characterized and were used to pretreat macrophages induced with oxidized low-density lipoprotein (ox-LDL). Indicators linked to ferroptosis and oxidative stress were detected. Finally, the expression of nuclear factor erythroid -related factor 2 (NRF2) was evaluated. ASX intervention significantly delayed the progression of AS plaques, characterized by reductions in plaque area and increased collagen fibers. The observed improvements in AS were consistent with statins. ASX-PLGA NPs demonstrate good safety and stability and have better therapeutic effects than ASX alone. Indicators linked to ferroptosis and oxidative stress were significantly improved in groups containing ASX in vivo and vitro. Additionally, ASX facilitated the nuclear translocation of NRF2, which could be attenuated with ML385, a specific inhibitor of NRF2. ASX-PLGA NPs have better therapeutic effects than ASX alone. The regulation of NRF2/SLC7A11/GPX4 represents a novel mechanism by which ASX can counteract ferroptosis and impede AS progression.

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: Recent studies have shown that the 4G/5G insertion/deletion variant ofSERPINE1(rs1799889) is closely linked to coronary artery disease (CAD). This study aims to clarify the effects of the rs1799889 variant on lipid levels and to insight into the mechanisms underlying the rs1799889 variant and CAD.Methods and Results: By searching PubMed and the Cochrane databases for studies published before 31 October 2021, 40 studies conducted on a total of 13,117 subjects were included for the analysis. The consistent findings for the effects of the 5G allele of rs1799889 variant on lipid metabolism were the significantly decreased triglycerides (TG) [standardized mean difference (SMD) = –0.12, 95% CI = –0.21 to 0.03,P= 0.01], total cholesterol (TC) (SMD = –0.12, 95% CI = –0.17 to 0.06,P< 0.001), and low-density lipoprotein cholesterol (LDL-C) (SMD = –0.13, 95% CI = –0.23 to 0.03,P= 0.01) levels. Intriguingly, the significant effects of the rs1799889 variant on LDL-C (SMD = –0.15, 95% CI = –0.26 to 0.05,P< 0.01) and TC (SMD = –0.17, 95% CI = –0.27 to 0.07,P< 0.01) levels were primarily observed in the Asian population. However, the significant effect of the rs1799889 variant on high-density lipoprotein cholesterol (HDL-C) (SMD = 0.26, 95% CI = 0.03–0.48,P= 0.03) levels was detected only in female subjects.Conclusion: The rs1799889 variant ofSERPINE1is a protective genetic factor against CAD, the Asian population with the 5G allele of the rs1799889 variant may have a reduced CAD risk.

Accumulating evidence has shown that the rs738409 polymorphism of patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD). Since NAFLD has been reported to be associated with lipid metabolism, this study is conducted to explore whether the rs738409 polymorphism of PNPLA3 was associated with lipid levels. By searching PubMed and the Cochrane database from May 31, 2020, to June 30, 2021. Sixty-three studies (81 003 subjects) were included for the analysis. The consistent findings for the associations of rs738409 polymorphism with lipid levels were the significantly decreased triglycerides (TG) (SMD=−0.04, 95% CI=−0.07 to −0.01, p=0.02) and total cholesterol (TC) (SMD=−0.03, 95% CI=−0.05 to −0.01, p<0.01) levels. Subgroup analysis indicated that the associations of rs738409 polymorphism with TG and TC levels were stronger in Caucasians, obesity patients, and adult subjects than in Asians, T2DM patients, and children subjects. The rs738409 polymorphism of PNPLA3 was associated with lower TG and TC levels in Caucasians, obese and adult subjects, which may contribute to the reduced coronary artery disease (CAD) risk between PNPLA3 rs738409 polymorphism and CAD.

Summary: Background: Corona Virus Disease 2019 (COVID-19) pandemic is still a public health emergency of international concern. However, whether pregnancy and menopause impact the severity of COVID-19 remain unclear. Aim: This study is performed to investigate the truth. Design: Study appraisal and synthesis follows PRISMA guideline. Meta-analysis is performed in random-effects model. Methods: PubMed, Embase, Cochrane database, Central, CINAHL, ClinicalTrials.gov, WHO COVID-19 database and WHO-ICTRP are searched until 28 March 2023. Results: In total, 57 studies (4 640 275 COVID-19 women) were analyzed. Pregnant women were at a lower risk of severe COVID-19, intensive care unit (ICU) admission and disease mortality compared to those nonpregnant women with comparable comorbidities. In contrast, pregnant women with more prepregnancy comorbidities were at a higher risk of severe COVID-19, ICU admission and invasive mechanical ventilation (IMV). In addition, pregnant women with pregnancy complications had a significantly increased risk of severe COVID-19 and ICU admission. Menopause increased COVID-19 severity, IMV requirement and disease mortality. Hormone replacement therapy inhibited COVID-19 severity in postmenopausal women. Premenopausal and postmenopausal women had a lower chance of severe illness than age-matched men. The impact of pregnancy on COVID-19 severity was significant in Americans and Caucasians, whereas the effect of menopause on COVID-19 severity was only significant in Chinese. Conclusions: Pregnancy and menopause are protective and risk factors for severe COVID-19, respectively. The protective role of pregnancy on COVID-19 is minimal and could be counteracted or masked by prepregnancy or pregnancy comorbidities. The administration of estrogen and progesterone may prevent severe COVID-19.