Vincent L Chen, Antonino Oliveri, Chinmay Raut, Yanhua Chen, Kelly C Cushing-Damm, Elizabeth K Speliotes
{"title":"在社区队列中，TM6SF2-rs58542926 基因型对肝脏和心脏事件发生率的影响是相反的：TM6SF2 对肝脏和心脏结果的影响。","authors":"Vincent L Chen, Antonino Oliveri, Chinmay Raut, Yanhua Chen, Kelly C Cushing-Damm, Elizabeth K Speliotes","doi":"10.14309/ajg.0000000000003169","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and aims: </strong>TM6SF2-rs58542926-T is associated with increased cirrhosis and modestly decreased coronary artery disease prevalence. However, relative effects of TM6SF2 genotype on major adverse cardiovascular events (MACE) vs. liver-related events (LRE) is not known.</p><p><strong>Approach: </strong>We utilized the UK Biobank, a prospective cohort with genetic and inpatient diagnosis data. The primary predictor was TM6SF2-rs58542926 genotype and the primary outcomes were MACE and LRE. Effects were reported as subhazard ratios (sHR) and 10-year cumulative incidence by Fine-Gray competing risk analyses.</p><p><strong>Results: </strong>>430,000 individuals met inclusion criteria. TM6SF2-rs58542926-TT genotype (vs. CC) was associated with higher incidence of LRE (adjusted sHR 3.16, 95% confidence interval [CI] 1.86-5.37) and lower incidence of MACE (adjusted sHR for TT vs. CC genotype 0.76, 95% CI 0.63-0.91 ). In individuals with Fibrosis-4 (FIB4) <1.3, 1.3-2.67, and >2.67, 10-year LRE incidence in TM6SF2-rs58542926-TT vs. CC individuals was 0.08% vs. 0.06% (p>0.05), 0.81% vs. 0.20% (p<0.0001), and 10.5% vs. 3.4% (p=0.00094), respectively. The corresponding values for MACE were 3.8% vs. 5.1% (p=0.032), 6.4% vs. 8.2% (p=0.040), and 17.1% vs. 12.4% (p>0.05). The absolute decrease in MACE with rs58542926-TT (vs. CC) genotype exceeded the absolute increase in LRE in all groups but FIB4>2.67. Associations of TM6SF2 genotype with LRE/MACE were significant in men but not women. TM6SF2-rs58542926-T allele was also associated with increased hepatic steatosis and corrected T1 time by magnetic resonance imaging, with greater effect sizes in men than women.</p><p><strong>Conclusions: </strong>TM6SF2 genotype has opposite effects on LRE vs. MACE incidence, and absolute effects on MACE were greater except in those with highest FIB4 scores. Effects were strongest in men. These findings clarify implications of TM6SF2 genotype based on personalized clinical risk.</p>","PeriodicalId":7608,"journal":{"name":"American Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":8.0000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"TM6SF2-rs58542926 genotype has opposing effects on incidence of hepatic and cardiac events in a community cohort: TM6SF2 effects on liver and cardiac outcomes.\",\"authors\":\"Vincent L Chen, Antonino Oliveri, Chinmay Raut, Yanhua Chen, Kelly C Cushing-Damm, Elizabeth K Speliotes\",\"doi\":\"10.14309/ajg.0000000000003169\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and aims: </strong>TM6SF2-rs58542926-T is associated with increased cirrhosis and modestly decreased coronary artery disease prevalence. However, relative effects of TM6SF2 genotype on major adverse cardiovascular events (MACE) vs. liver-related events (LRE) is not known.</p><p><strong>Approach: </strong>We utilized the UK Biobank, a prospective cohort with genetic and inpatient diagnosis data. The primary predictor was TM6SF2-rs58542926 genotype and the primary outcomes were MACE and LRE. Effects were reported as subhazard ratios (sHR) and 10-year cumulative incidence by Fine-Gray competing risk analyses.</p><p><strong>Results: </strong>>430,000 individuals met inclusion criteria. TM6SF2-rs58542926-TT genotype (vs. CC) was associated with higher incidence of LRE (adjusted sHR 3.16, 95% confidence interval [CI] 1.86-5.37) and lower incidence of MACE (adjusted sHR for TT vs. CC genotype 0.76, 95% CI 0.63-0.91 ). In individuals with Fibrosis-4 (FIB4) <1.3, 1.3-2.67, and >2.67, 10-year LRE incidence in TM6SF2-rs58542926-TT vs. CC individuals was 0.08% vs. 0.06% (p>0.05), 0.81% vs. 0.20% (p<0.0001), and 10.5% vs. 3.4% (p=0.00094), respectively. The corresponding values for MACE were 3.8% vs. 5.1% (p=0.032), 6.4% vs. 8.2% (p=0.040), and 17.1% vs. 12.4% (p>0.05). The absolute decrease in MACE with rs58542926-TT (vs. CC) genotype exceeded the absolute increase in LRE in all groups but FIB4>2.67. Associations of TM6SF2 genotype with LRE/MACE were significant in men but not women. TM6SF2-rs58542926-T allele was also associated with increased hepatic steatosis and corrected T1 time by magnetic resonance imaging, with greater effect sizes in men than women.</p><p><strong>Conclusions: </strong>TM6SF2 genotype has opposite effects on LRE vs. MACE incidence, and absolute effects on MACE were greater except in those with highest FIB4 scores. Effects were strongest in men. These findings clarify implications of TM6SF2 genotype based on personalized clinical risk.</p>\",\"PeriodicalId\":7608,\"journal\":{\"name\":\"American Journal of Gastroenterology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":8.0000,\"publicationDate\":\"2024-10-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.14309/ajg.0000000000003169\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.14309/ajg.0000000000003169","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
TM6SF2-rs58542926 genotype has opposing effects on incidence of hepatic and cardiac events in a community cohort: TM6SF2 effects on liver and cardiac outcomes.
Background and aims: TM6SF2-rs58542926-T is associated with increased cirrhosis and modestly decreased coronary artery disease prevalence. However, relative effects of TM6SF2 genotype on major adverse cardiovascular events (MACE) vs. liver-related events (LRE) is not known.
Approach: We utilized the UK Biobank, a prospective cohort with genetic and inpatient diagnosis data. The primary predictor was TM6SF2-rs58542926 genotype and the primary outcomes were MACE and LRE. Effects were reported as subhazard ratios (sHR) and 10-year cumulative incidence by Fine-Gray competing risk analyses.
Results: >430,000 individuals met inclusion criteria. TM6SF2-rs58542926-TT genotype (vs. CC) was associated with higher incidence of LRE (adjusted sHR 3.16, 95% confidence interval [CI] 1.86-5.37) and lower incidence of MACE (adjusted sHR for TT vs. CC genotype 0.76, 95% CI 0.63-0.91 ). In individuals with Fibrosis-4 (FIB4) <1.3, 1.3-2.67, and >2.67, 10-year LRE incidence in TM6SF2-rs58542926-TT vs. CC individuals was 0.08% vs. 0.06% (p>0.05), 0.81% vs. 0.20% (p<0.0001), and 10.5% vs. 3.4% (p=0.00094), respectively. The corresponding values for MACE were 3.8% vs. 5.1% (p=0.032), 6.4% vs. 8.2% (p=0.040), and 17.1% vs. 12.4% (p>0.05). The absolute decrease in MACE with rs58542926-TT (vs. CC) genotype exceeded the absolute increase in LRE in all groups but FIB4>2.67. Associations of TM6SF2 genotype with LRE/MACE were significant in men but not women. TM6SF2-rs58542926-T allele was also associated with increased hepatic steatosis and corrected T1 time by magnetic resonance imaging, with greater effect sizes in men than women.
Conclusions: TM6SF2 genotype has opposite effects on LRE vs. MACE incidence, and absolute effects on MACE were greater except in those with highest FIB4 scores. Effects were strongest in men. These findings clarify implications of TM6SF2 genotype based on personalized clinical risk.
期刊介绍：
Published on behalf of the American College of Gastroenterology (ACG), The American Journal of Gastroenterology (AJG) stands as the foremost clinical journal in the fields of gastroenterology and hepatology. AJG offers practical and professional support to clinicians addressing the most prevalent gastroenterological disorders in patients.
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