Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Salzburg, Austria.
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Wien Klin Wochenschr. 2024 May;136(9-10):251-257. doi: 10.1007/s00508-023-02196-2. Epub 2023 Apr 27.
Single-nucleotide-polymorphisms in PNPLA3-rs738409 and the TM6SF2-rs58542926, associated with metabolic-dysfunction-associated fatty liver disease (MAFLD), have been discussed as potentially protective for cardiovascular diseases. Therefore, we aimed to study the associations of PNPLA3/TM6SF2 variants with MAFLD and cardiovascular risk in a population-based sample of asymptomatic patients.
The study cohort comprised 1742 patients of European decent aged 45-80 years from a registry study undergoing screening colonoscopy for colorectal cancer between 2010 and 2014. SCORE2 and Framingham risk score calculated to assess cardiovascular risk. Data on survival were obtained from the national death registry RESULTS: Half of included patients were male (52%, 59 ± 10 years), 819 (47%) carried PNPLA3‑G and 278 (16%) TM6SF2-T-alleles. MAFLD (PNPLA3‑G-allele: 46% vs. 41%, p = 0.041; TM6SF2‑T-allele: 54% vs. 42%, p < 0.001) was more frequent in patients harbouring risk alleles with both showing independent associations with MAFLD on multivariable binary logistic regression analysis. While median Framingham risk score was lower in PNPLA3‑G-allele carriers (10 vs. 8, p = 0.011), SCORE2 and established cardiovascular diseases were similar across carriers vs. non-carriers of the respective risk-alleles. During a median follow-up of 9.1 years, neither PNPLA3‑G-allele nor TM6SF2‑T-allele was associated with overall nor with cardiovascular mortality.
Carriage of PNPLA3/TM6SF2 risk alleles could not be identified as significant factor for all-cause or cardiovascular mortality in asymptomatic middle-aged individuals undergoing screening colonoscopy.
与代谢相关脂肪性肝病（MAFLD）相关的单核苷酸多态性（PNPLA3-rs738409 和 TM6SF2-rs58542926）已被讨论为可能对心血管疾病具有保护作用。因此，我们旨在研究 PNPLA3/TM6SF2 变体与无症状患者人群中的 MAFLD 和心血管风险的关联。
该研究队列包括 2010 年至 2014 年间接受结直肠癌筛查结肠镜检查的 1742 名欧洲裔 45-80 岁的患者。使用 SCORE2 和 Framingham 风险评分来评估心血管风险。生存数据来自国家死亡登记处。
纳入的患者中有一半是男性（52%，59±10 岁），819 名（47%）携带 PNPLA3-G 等位基因，278 名（16%）携带 TM6SF2-T 等位基因。MAFLD（携带 PNPLA3-G 等位基因：46%比 41%，p=0.041；携带 TM6SF2-T 等位基因：54%比 42%，p<0.001）在携带风险等位基因的患者中更为常见，两者在多变量二项逻辑回归分析中均显示与 MAFLD 独立相关。虽然 PNPLA3-G 等位基因携带者的Framingham 风险评分中位数较低（10 比 8，p=0.011），但 SCORE2 和已确立的心血管疾病在携带者和非携带者之间相似。在中位随访 9.1 年期间，PNPLA3-G 等位基因或 TM6SF2-T 等位基因均与全因或心血管死亡率无关。
在接受筛查结肠镜检查的无症状中年个体中，PNPLA3/TM6SF2 风险等位基因不能被确定为全因或心血管死亡率的重要因素。
