A missing link in cholesterol absorption: Cholesterol is important for general health, but too much can build up in artery walls and cause cardiovascular disease. Low-density lipoprotein cholesterol (LDL-C) is often referred to as “bad cholesterol”; keeping LDL-C within stringent limits is recommended to reduce the risk of heart attack and stroke. Zhang et al. discovered that some individuals have an inherited frameshift mutation in the LIMA1 gene (also known as EPLIN or SREBP3 ). The gene has not been linked to lipid metabolism before, but altered LIMA1 was found to maintain low plasma LDL-C by reducing the absorption of cholesterol through the intestine. Pharmacological targeting through the LIMA1 pathway might thus provide a strategy to improve heart health. Science , this issue p. 1087

Angiopoietin-like protein 3 is essential in lipid metabolism regulation. However, the efficacy and safety of evinacumab (angiopoietin-like protein 3 inhibition drug) for hypercholesterolemia treatment is unknown. In this study, a meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of evinacumab. RCTs published between January 1, 2000, and November 1, 2020, were obtained from PubMed, Embase, and Cochrane Library. All RCTs evaluating the efficacy and safety of evinacumab were included without language restrictions. Our primary end points included the percent change of low-density lipoprotein cholesterol (LDL-C) from baseline and the incidence of at least one treatment emergent adverse events including nasopharyngitis, influenza-like illness, headache, dizziness, injection-site reaction, increased aspartate aminotransferase, increased alanine aminotransferase, and any other discomfort during treatments. Percentage changes of triglycerides and high-density lipoprotein cholesterol (HDL-C) from baseline indicated secondary end points. A random-effects model was used to assess pooled data if there was moderate to high heterogeneity between studies. Four studies with 5 RCTs (568 participants) were identified. Evinacumab significantly reduced LDL-C [mean difference (MD) −33.123%, 95% confidence interval (CI), −48.639% to −17.606%, P < 0.0001], triglycerides (MD −50.959%, 95% CI, −56.555% to −45.362%, P < 0.0001), and HDL-C (MD −12.773%, 95% CI, −16.359% to −9.186%, P < 0.0001) compared with placebo. The incidence of at least 1 treatment emergent adverse events was not significantly different between evinacumab and placebo groups (relative risk 1.080, 95% CI, 0.901–1.296, P = 0.405). Evinacumab decreased triglycerides, LDL-C, and HDL-C without significant adverse effects, indicating that it can be a therapeutic strategy for hypercholesterolemia.

CYP17A1 gene encodes P450c17 proteins, which is a key enzyme that catalyzes the formation of sex hormones. Many clinical studies showed that sex hormones levels play an important role in the pathogenesis of coronary artery disease (CAD). However, the relationship between CYP17A1 genetic polymorphisms and CAD remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with CAD in a Han population of China. A total of 997 people include 490 patients and 507 controls were selected for the present study. Five single-nucleotide polymorphisms (SNPs) (rs4919686, rs1004467, rs4919687, rs10786712, and rs2486758) were genotyped by using the real-time PCR (TaqMan) method. For men, the rs10786712 was found to be associated with CAD in a recessive model (P = 0.016), after adjustment of the major confounding factors, the significant difference was retained (OR = 1.644, 95% confidence interval [CI]: 1.087-2.488, P = 0.019). For women, the rs1004467 was also found to be associated with CAD in a dominant model (P = 0.038), the difference remained statistically significant after multivariate adjustment (OR = 1.623, 95% CI: 1.023-2.576, P = 0.040). The distribution of rs4919687 genotypes showed a significant difference between CAD and control participants in a recessive model (P = 0.019), the significant difference was retained after adjustment for covariates (OR = 0.417, 95% CI: 0.188-0.926, P = 0.032). Rs1004467, rs4919687, rs10786712 of CYP17A1 gene are associated with CAD in Han population of China. The TT genotype of rs10786712 could be a protective genetic marker of CAD in men. The CC genotype of rs1004467 and the AA genotype of rs4919687 could be risk genetic markers of CAD in women. However, large sample size study including other SNPs of CYP17A1 should be performed in future studies.

Ethnic differences in non-invasive measurements of carotid atherosclerosis are being increasingly reported, but the association between carotid atherosclerosis and different subtypes of hypertension in adult populations is not fully understood in different ethnicities. We aimed to investigate the association of carotid atherosclerosis with different subtypes of hypertension in different ethnicities in Xinjiang, a northwestern province in China. A total of 14,618 participants (5,757 Hans, 4,767 Uygurs, and 4,094 Kazakhs) from 26 villages of seven cities in Xinjiang were randomly selected from the Cardiovascular Risk Survey conducted during 2007 and 2010. A standard questionnaire, a physical examination and biochemical tests were employed. The mean common carotid intima-media thickness (CIMT) for the 14,618 participants was 0.86±0.003 mm. The CIMT gradually increased with age. Men (0.92±0.005 mm) had a higher CIMT than women (0.81±0.004 mm). The Uygur participants (0.82±0.006 mm) had a lower CIMT than the Han (0.88±0.005 mm) and Kazakh participants (0.88±0.005 mm). The overall prevalences of carotid intimal thickening and carotid plaques were 12.4% and 9.7%, respectively. The prevalence of CIMT varied for the different subtypes of hypertension. Multivariate logistic regression analysis showed different risk factors for abnormal CIMT in different ethnicities. The associations between abnormal CIMT and the different subtypes of hypertension within different ethnic backgrounds were also different. The risk factors for abnormal CIMT included systolic-diastolic hypertension (SDH) in Han participants (OR: 1.323, 95% CI: 1.100–1.590), SDH (OR: 1.426, 95% CI: 1.160–1.753) and isolated-systolic hypertension (ISH) (OR: 1.844, 95% CI: 1.470–2.313) in Uygur participants, and isolated-diastolic hypertension (IDH) (OR: 1.536, 95% CI: 1.170–2.016) in Kazakh participants. There was an ethnic difference in the prevalence of abnormal CIMT in Xinjiang, a northwestern province in China. The associations between abnormal CIMT and the subtypes of hypertension varied among the different ethnic groups. Among the studied populations, Han participants with SDH, Uygur participants with SDH and ISH, and Kazakh with IDH were more likely to suffer carotid atherosclerosis than those with other subtypes of hypertension. Participants with different ethnic backgrounds had different sets of risk factors for abnormal CIMT.

It has been reported that oxidative stress is a factor in cerebral infarction (CI). Extracellular superoxide dismutase (EC-SOD) is important in preventing oxidative stress, and the cerebral infarct size of EC-SOD knockout mice is significantly larger than that in wild-type controls. The aim of this study was to investigate the relationship between CI and the human EC-SOD gene using single-nucleotide polymorphism (SNP) in Japanese individuals. We selected five single-nucleotide polymorphisms of the human EC-SOD gene (rs13306703, rs699473, rs17881426, rs2536512 and rs1799895) and performed a case-control study using each SNP and haplotype in 175 CI patients (103 men, 72 women) and 299 controls (144 men and 155 women). Among women, there were significant differences between the CI and control group in overall distribution of alleles for rs699473 (men: OR=1.031, 95% CI: 0.705-1.506, women: OR=1.916, 95% CI: 1.196-3.071) and rs2536512 (men: OR=0.774, 95% CI: 0.523-1.146, women: OR=2.107, 95% CI: 1.227-3.462). In a haplotype-based case control on rs13306703, rs699473 and rs1799895 in women, the frequency of the C-C-C haplotype was significantly higher in the CI group than in the control group (men; 51.5% vs 51.4% p=0.9865, women; 62.5% vs 49.7% p=0.0108). Multiple logistic regression analysis also revealed a significant difference in C-C-C haplotype in women, even after adjustment for confounding factors (OR=2.205, 95% CI: 1.069-4.552 p=0.032). The C-C-C haplotypes could be genetic markers for CI, and the EC-SOD gene may be a susceptibility gene for CI in women.

Background Coronary heart disease has become the leading cause of death in developed countries, and dyslipidemia is closely associated with the risk of cardiovascular disease. Dyslipidemia is caused by the abnormal regulation of several genes and signaling pathways, and dyslipidemia is influenced mainly by genetic variation. AMFR, FBXW7, INSIG1, INSIG2, and MBTPS1 genes are associated with lipid metabolism. In a recent GWAS study, the GRINA gene has been reported to be associated with dyslipidemia, but its molecular mechanism has not been thoroughly investigated. The correlation between the DNA methylation of these genes and lipid metabolism has not been studied. This study aimed to examine the relationship between the DNA methylation of these genes and the risk of dyslipidemia by comparing the methylation levels of dyslipidemia and control samples. Methods A case-control research method was used in this study. The patient’s blood samples were collected at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University. In the Xinjiang Han population, 100 cases of hyperlipidemia and 80 cases of the control group were selected. The two groups were age and gender-matched. Quantitative methylation analysis of CpG sites in the gene promoter regions of six genes was performed by Solexa high-throughput sequencing. Results The DNA methylation levels of 23 CpG sites in six genes were shown to be associated with hyperlipidemia, and a total of 20 DNA methylation haplotypes showed statistically significant differences between the two groups. When compared with the control group, the dyslipidemia group had significantly higher levels of methylation in the GRINA gene (2.68 vs 2.36, P = 0.04). Additionally, we also discovered a significant methylation haplotype of GRINA (P = 0.017). Conclusion The findings of this study reveal that the DNA methylation of GRINA increases the risk for dyslipidemia in humans.