{"title":"肝硬化酒精使用障碍患者长分散核苷酸元件和醛脱氢酶的低甲基化。","authors":"Bhagyalakshmi Shankarappa, Jayant Mahadevan, Pratima Murthy, Meera Purushottam, Biju Viswanath, Sanjeev Jain, Harshad Devarbhavi, Ashok Mysore Visweswariah","doi":"10.1089/dna.2022.0669","DOIUrl":null,"url":null,"abstract":"<p><p>Alcohol use disorder (AUD) and cirrhosis are key outcomes of excessive alcohol use, and a genetic influence in these outcomes is increasingly recognized. While 80-90% of heavy alcohol users show evidence of fatty liver, only 10-20% progress to cirrhosis. There is currently no clear understanding of the causes of this difference in progression. The aim of this study is to evaluate genetics and epigenetics at the aldehyde dehydrogenase (<i>ALDH2)</i> locus in patients with AUD and liver complications. Study participants were inpatients from the clinical services of Gastroenterology and Psychiatry at St. John's Medical College Hospital (SJMCH) and the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Men diagnosed as having AUD with cirrhosis (AUDC+ve, <i>N</i> = 136) and AUD without cirrhosis (AUDC-ve, <i>N</i> = 107) were assessed. FibroScan/sonographic evidence was used to rule out fibrosis in the AUDC-ve group. Genomic DNA was used for genotyping at the <i>ALDH2</i> (rs2238151) locus. A subset of 89 samples was used for DNA methylation (AUDC+ve, <i>N</i> = 44; and AUDC-ve, <i>N</i> = 45) analysis at long interspersed nucleotide element 1 (<i>LINE-1</i>) and <i>ALDH2</i> cytosine-phosphate-guanine (CpG) loci by pyrosequencing. <i>ALDH2</i> DNA methylation was significantly lower in the AUDC+ve group compared with the AUDC-ve group (<i>p</i> < 0.001). Lower methylation was associated with a risk allele (T) of the <i>ALDH2</i> locus (rs2238151) (<i>p</i> = 0.01). Global (<i>LINE-1</i>) DNA methylation levels were also significantly lower in the AUDC+ve group compared with the AUDC-ve group (<i>p</i> = 0.01). Compromised global methylation (<i>LINE-1)</i> and hypomethylation at the <i>ALDH2</i> gene was observed in patients with cirrhosis compared with those without cirrhosis. DNA methylation could be explored as a biomarker for cirrhosis and liver complications.</p>","PeriodicalId":11248,"journal":{"name":"DNA and cell biology","volume":"42 7","pages":"364-371"},"PeriodicalIF":2.6000,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Hypomethylation of Long Interspersed Nucleotide Elements and Aldehyde Dehydrogenase in Patients of Alcohol Use Disorder with Cirrhosis.\",\"authors\":\"Bhagyalakshmi Shankarappa, Jayant Mahadevan, Pratima Murthy, Meera Purushottam, Biju Viswanath, Sanjeev Jain, Harshad Devarbhavi, Ashok Mysore Visweswariah\",\"doi\":\"10.1089/dna.2022.0669\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Alcohol use disorder (AUD) and cirrhosis are key outcomes of excessive alcohol use, and a genetic influence in these outcomes is increasingly recognized. While 80-90% of heavy alcohol users show evidence of fatty liver, only 10-20% progress to cirrhosis. There is currently no clear understanding of the causes of this difference in progression. The aim of this study is to evaluate genetics and epigenetics at the aldehyde dehydrogenase (<i>ALDH2)</i> locus in patients with AUD and liver complications. Study participants were inpatients from the clinical services of Gastroenterology and Psychiatry at St. John's Medical College Hospital (SJMCH) and the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Men diagnosed as having AUD with cirrhosis (AUDC+ve, <i>N</i> = 136) and AUD without cirrhosis (AUDC-ve, <i>N</i> = 107) were assessed. FibroScan/sonographic evidence was used to rule out fibrosis in the AUDC-ve group. Genomic DNA was used for genotyping at the <i>ALDH2</i> (rs2238151) locus. A subset of 89 samples was used for DNA methylation (AUDC+ve, <i>N</i> = 44; and AUDC-ve, <i>N</i> = 45) analysis at long interspersed nucleotide element 1 (<i>LINE-1</i>) and <i>ALDH2</i> cytosine-phosphate-guanine (CpG) loci by pyrosequencing. <i>ALDH2</i> DNA methylation was significantly lower in the AUDC+ve group compared with the AUDC-ve group (<i>p</i> < 0.001). Lower methylation was associated with a risk allele (T) of the <i>ALDH2</i> locus (rs2238151) (<i>p</i> = 0.01). Global (<i>LINE-1</i>) DNA methylation levels were also significantly lower in the AUDC+ve group compared with the AUDC-ve group (<i>p</i> = 0.01). Compromised global methylation (<i>LINE-1)</i> and hypomethylation at the <i>ALDH2</i> gene was observed in patients with cirrhosis compared with those without cirrhosis. DNA methylation could be explored as a biomarker for cirrhosis and liver complications.</p>\",\"PeriodicalId\":11248,\"journal\":{\"name\":\"DNA and cell biology\",\"volume\":\"42 7\",\"pages\":\"364-371\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2023-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"DNA and cell biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/dna.2022.0669\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"DNA and cell biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/dna.2022.0669","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 1
摘要
酒精使用障碍(AUD)和肝硬化是过度饮酒的主要结果,遗传因素对这些结果的影响越来越被认识到。虽然80-90%的重度酒精使用者表现出脂肪肝的迹象,但只有10-20%进展为肝硬化。目前对这种进展差异的原因还没有明确的认识。本研究的目的是评估AUD和肝脏并发症患者醛脱氢酶(ALDH2)位点的遗传学和表观遗传学。研究参与者是来自印度班加罗尔圣约翰医学院医院(SJMCH)和国家精神卫生和神经科学研究所(NIMHANS)胃肠病学和精神病学临床服务的住院患者。对诊断为AUD合并肝硬化(AUDC+ve, N = 136)和AUD无肝硬化(AUDC-ve, N = 107)的男性进行评估。纤维扫描/超声证据用于排除AUDC-ve组的纤维化。利用基因组DNA在ALDH2 (rs2238151)位点进行基因分型。89个样本的子集用于DNA甲基化(AUDC+ve, N = 44;和AUDC-ve, N = 45)分析了长点缀核苷酸元件1 (LINE-1)和ALDH2胞嘧啶-磷酸-鸟嘌呤(CpG)位点。与AUDC-ve组相比,AUDC+ve组ALDH2 DNA甲基化显著降低(p ALDH2位点(rs2238151)) (p = 0.01)。与AUDC-ve组相比,AUDC+ve组的全球(LINE-1) DNA甲基化水平也显著降低(p = 0.01)。与没有肝硬化的患者相比,肝硬化患者观察到ALDH2基因的整体甲基化(LINE-1)和低甲基化。DNA甲基化可以作为肝硬化和肝脏并发症的生物标志物。
Hypomethylation of Long Interspersed Nucleotide Elements and Aldehyde Dehydrogenase in Patients of Alcohol Use Disorder with Cirrhosis.
Alcohol use disorder (AUD) and cirrhosis are key outcomes of excessive alcohol use, and a genetic influence in these outcomes is increasingly recognized. While 80-90% of heavy alcohol users show evidence of fatty liver, only 10-20% progress to cirrhosis. There is currently no clear understanding of the causes of this difference in progression. The aim of this study is to evaluate genetics and epigenetics at the aldehyde dehydrogenase (ALDH2) locus in patients with AUD and liver complications. Study participants were inpatients from the clinical services of Gastroenterology and Psychiatry at St. John's Medical College Hospital (SJMCH) and the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Men diagnosed as having AUD with cirrhosis (AUDC+ve, N = 136) and AUD without cirrhosis (AUDC-ve, N = 107) were assessed. FibroScan/sonographic evidence was used to rule out fibrosis in the AUDC-ve group. Genomic DNA was used for genotyping at the ALDH2 (rs2238151) locus. A subset of 89 samples was used for DNA methylation (AUDC+ve, N = 44; and AUDC-ve, N = 45) analysis at long interspersed nucleotide element 1 (LINE-1) and ALDH2 cytosine-phosphate-guanine (CpG) loci by pyrosequencing. ALDH2 DNA methylation was significantly lower in the AUDC+ve group compared with the AUDC-ve group (p < 0.001). Lower methylation was associated with a risk allele (T) of the ALDH2 locus (rs2238151) (p = 0.01). Global (LINE-1) DNA methylation levels were also significantly lower in the AUDC+ve group compared with the AUDC-ve group (p = 0.01). Compromised global methylation (LINE-1) and hypomethylation at the ALDH2 gene was observed in patients with cirrhosis compared with those without cirrhosis. DNA methylation could be explored as a biomarker for cirrhosis and liver complications.
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