Recurrent missense variants in clonal hematopoiesis-related genes present in the general population

Clonal hematopoiesis (CH) consists in an abnormal expansion of a hematopoietic stem cell bearing an advantageous somatic variant. A survey of known recurrent somatic missense variants in DNMT3A, SF3B1, SRSF2, and TP53, some of the most prominent genes underlying CH of indeterminate potential (CHIP), in gnomAD noncancer database shows the presence of 73 variants. Many of them reach frequencies higher than 0.01% in various populations and, in many cases, are enriched in specific populations. Consistent with a potential involvement in CHIP, we found that the age distribution of the carriers is shifted towards old ages. Moreover, the variant allele frequencies are on average lower than 50%, expected for germline heterozygous variants. The pervasive presence of some of such variants in blood DNA from elder individuals is compatible with CHIP of somatic origin. On practical grounds, CHIP can lead to misclassification of somatic variants in cancer-predisposition genes as inherited, which bear consequences for the affected individuals and their families.     

Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes

Background and aimsIncreased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2^EK; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.Methods and resultsMales with recent-onset type 2 diabetes with (TM6SF2^EK: n = 16) or without (TM6SF2^EE: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-²H₂]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with ¹H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2^EK had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2^EE. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2^EE only.ConclusionsThe TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.     

再造生血胶囊联合琥珀酸亚铁治疗气血两虚证型缺铁性贫血的疗效观察

目的 探讨再造生血胶囊联合琥珀酸亚铁治疗气血两虚证型缺铁性贫血的临床效果。方法 选取2019年1月—2023年3月太和县人民医院收治的120例气血两虚缺铁性贫血患者，随机分为对照组（60例）和治疗组（60例）。对照组口服琥珀酸亚铁片，0.1 g/次，3次/d。治疗组在对照组基础上口服再造生血胶囊，5粒/次，3次/d。两组患者治疗3个月。观察两组患者临床疗效，比较治疗前后两组铁离子（SI）、血清铁蛋白（SF）和血红蛋白（HGB）水平及中医证候积分。结果 治疗后，治疗组患者总有效率较对照组显著升高（98.33% vs 88.33%，P＜0.05）。治疗后，两组SI、SF及HGB水平显著高于治疗前（P＜0.05），且治疗组明显高于对照组（P＜0.05）。治疗后，两组中医证候积分显著低于治疗前（P＜0.05），且治疗组明显低于对照组（P＜0.05）。结论 再造生血胶囊联合琥珀酸亚铁可有效提高气血两虚证型缺铁性贫血患者铁蛋白及血红蛋白水平，以及改善此类患者中医证候。     

SF、TSAT、Hcy与慢性心力衰竭伴贫血患者EPO低反应性相关性及临床意义

目的 探讨铁蛋白（serum ferritin，SF）、转铁蛋白饱和度（transferrin saturation，TSAT）、同型半胱氨酸（Homocysteine，Hcy）与慢性心力衰竭（chronic heart failure，CHF）伴贫血患者促红细胞生成素（erythropoietin，EPO）低反应性相关性及临床意义。方法选取2019年4月～2021年12月252例CHF伴贫血患者，根据患者EPO反应性分为低反应组、非低反应组，比较两组一般资料、SF、TSAT、Hcy，应用Spearman分析SF、TSAT、Hcy与美国纽约心脏病学会心功能分级（New York Heart Association，NYHA）关系，采用多因素Logistic回归方程分析EPO低反应性相关影响因素，采用受试者工作特征曲线（Receiver operating characteristic，ROC）及ROC下面积（Area under the curve，AUC）分析SF、TSAT、Hcy预测EPO低反应性价值。结果 低反应组NYHA分级与非低反应组比较，差异有统计学意义（P＜0.05）；低反应组SF、TSAT低于非低反应组，Hcy高于非低反应组（P＜0.05）；SF、TSAT与心功能NYHA分级呈负相关（r=-0.742、-0.751，P均＜0.001），Hcy与心功能NYHA分级呈正相关（r=0.800，P＜0.001）；NYHA分级Ⅳ级、血红蛋白、SF、TSAT、Hcy均是EPO低反应性的相关影响因素（P＜0.05）；SF、TSAT联合Hcy预测EPO低反应性的AUC为0.909，大于单独的SF（0.733）、TSAT（0.752）、Hcy（0.724）。结论 SF、TSAT、Hcy与CHF伴贫血患者EPO低反应性及心功能有关，联合检测可作为预测EPO反应性一种方法，为临床治疗提供参考。