Cardiovascular safety of genetically proxied interleukin-5 inhibition: A mendelian randomization study

Interleukin-5 (IL-5) inhibitors have revolutionized the management of eosinophilic asthma. However, IL-5 is thought to play a protective role in atherosclerosis, and cardiovascular safety data for IL-5i are scarce. We used population-level data to examine the association between genetically proxied IL-5i and the risk of cardiovascular diseases. Genetic instruments for IL-5i were selected from a genome-wide association study of eosinophil count in 563,946 individuals. Genetic association data for coronary artery disease were obtained from 60,801 cases, 40,585 stroke cases, 7988 venous thromboembolism cases, and up to 406,111 controls. We used the inverse-variance weighted method and a series of sensitivity analyses. Nine genetic variants were selected to instrument IL-5i. Genetically proxied IL-5i was not associated with the risk of coronary heart disease (OR 0.82, 95%CI 0.65–1.03), stroke (OR 1.10; 0.95–1.27), or venous thromboembolism (OR 0.87; 0.64–1.17). We found no genetic evidence to suggest that IL-5i affects the risk of adverse cardiovascular and thromboembolic events.     

The correlations among racial/ethnic groups,hypertriglyceridemia, thrombosis,and mortality in hospitalized patients with COVID-19

Reports of racial and ethnic disparities regarding both rates of infection of the SARS-CoV-2 virus and morbidity of the coronavirus disease-19 (COVID-19) contain profound differences depending on the population. Our previous study has shown that patients with COVID-19 who developed hypertriglyceridemia during hospitalization have a 2.3 times higher mortality rate. However, whether the correlation between hypertriglyceridemia and mortality has disparity among different racial and ethnic groups is unknown.In this study, we investigated the impact of race/ethnicity on the correlation between hypertriglyceridemia and mortality in hospitalized patients with COVID-19. De-identified information from 904 hospitalized patients diagnosed with COVID-19 between March 2020 and June 2021 were extracted from the Medical College of Wisconsin Clinical Data Warehouse. A multivariable regression analysis suggested that the Asians and non-White Hispanics had 4 or 3.9 times higher mortality rate, respectively, after adjusting for age, morbid obesity (BMI ≥40), and gender. The hypertriglyceridemia (≥150 mg/dL) was associated with higher mortality, after adjusting for age, gender, and morbid obesity. The baseline hypertriglyceridemia occurrence had relevantly more consistent percentages among all racial/ethnic groups. However, non-White Hispanic and Asian patients had the highest frequencies of peak hypertriglyceridemia occurrence during hospitalization. The peak hypertriglyceridemia developed during hospitalization correlates with the incidence of thrombosis after adjusting for morbid obesity, age, and sex. In summary, in this retrospective study of 904 hospitalized COVID-19 patients, Asians and non-White Hispanics had a greater likelihood of developing hypertriglyceridemia during hospitalization and mortality than White patients.     

全基因组关联分析在消化系肿瘤中的研究进展

全基因组关联分析(genome-wide association study,GWAS)是应用人类基因组中单核苷酸多态性(single nucleotide polymorphism,SNP)为标记进行分析,以期发现影响复杂性疾病发生的遗传特征的一种新策略.因其可在全基因组范围内进行整体研究,能够一次性对疾病与基因的关联进行轮廓性概览,所以在过去的5年中,全基因组关联研究方法已被证明是研究复杂疾病一种有效手段.近年,各国科学家运用全基因组关联分析在人类肿瘤,特别是在消化系肿瘤的研究中取得了一系列重要的研究成果,本文将综述消化系肿瘤GWAS研究进展,并展望GWAS所面临的挑战及可能的解决策略.     

亚甲基四氢叶酸还原酶与肺癌的关联性研究

目的研究中国大陆人群亚甲基四氢叶酸还原酶（MTHFR）基因遗传位点C677T和A1298C多态性与肺癌的关联性。方法通过PubMed和CNKI等数据库检索有关MTHFR基因与肺癌的文献,收集和整理中国大陆人群MTHFR基因遗传位点C677T和A1298C与肺癌有关4 781例数据,进行Meta分析和关联性研究。结果 MTHFR基因遗传位点C677T的等位基因分布和基因型分布对应的假设检验的概率分别为2.6×10-3、9.4×10-3,表明病例对照差异有统计学意义（P〈0.05）;Meta分析对等位基因T的优势比OR值（95%CI）为1.28（1.16～1.41）。遗传位点A1298C的等位基因分布对应的假设检验概率分别为0.713和0.944,说明假设检验差异无统计学意义（P〉0.05）,Meta分析对等位基因A的优势比OR值（95%CI）为1.04（0.85～1.27）。结论 MTHFR基因的单核苷酸C677T多态性是中国大陆人群肺癌的遗传变异位点,A1298C多态性不是中国大陆人群肺癌的风险因素。     

儿童自闭症的遗传学研究进展

自闭症是一种以语言发育障碍、社会交往障碍及兴趣范围狭窄、行为刻板为主要特征的神经发育性疾病.通过同胞对和家系研究表明,其遗传度可高达90%.本文对近年来在自闭症遗传学研究方面的进展进行了论述,着重介绍目前的一些研究手段和分析方法,包括细胞遗传学、候选基因、连锁分析、拷贝数变异以及全基因组关联分析等研究.     

A genetic link between type 2 diabetes and prostate cancer

Epidemiological studies suggest that men with type 2 diabetes are less likely than non-diabetic men to develop prostate cancer. The cause of this association is not known. Recent genetic studies have highlighted a potential genetic link between the two diseases. Two studies have identified a version (allele) of a variant in the HNF1B (also known as TCF2) gene that predisposes to type 2 diabetes, and one of them showed that the same allele protects men from prostate cancer. Other, separate, studies have identified different variants in the JAZF1 gene, one associated with type 2 diabetes, another associated with prostate cancer. These findings are unlikely to completely explain the epidemiological association between the two diseases but they provide new insight into a possible direct causal link, rather than one that is confounded or biased in some way.     

血清TSH水平相关的遗传学研究进展

甲状腺激素在机体的牛理及代谢过程巾发挥重要作用.作为评价甲状腺功能的敏感指标,血清促甲状腺素(TSH)浓度在个体之间差异明显并且主要由遗传因素所决定.在经历了传统的连锁分析及候选基因关联分析之后,全基因组关联分析(GWAS)在研究血清TSH易感基因过程中取得了重大进展,并发现了许多新的易感位点.本文主要综述与血清TSH水平相关的基因,并对这些研究的未来进行了展望.