Scholarlink

Background <p>Gallstone disease (GSD) is a prevalent chronic hepatobiliary condition characterized by impaired metabolism of cholesterol, bilirubin, and bile acids. Gallstones are categorized as cholesterol, pigment (black and brown), or mixed stones. Genetic predisposition accounts for approximately 25% of cases, with multiple variants influencing GSD susceptibility.</p> Objective <p>This study investigates the association of <i>UGT1A1 </i>(<i>rs6742078</i>) and <i>ABCG8</i> (<i>rs11887534</i>) polymorphisms with GSD through a meta-analysis, bioinformatics assessment of non-synonymous SNPs (nsSNPs).</p> Methods <p>A systematic review of studies (<i>UGT1A1</i> and <i>ABCG8</i> from January 2000 to January 2020) was conducted using databases such as PubMed, Embase, Scopus, and Web of Science. Meta-analyses pooled data from 6492 cases and 59,635 controls for <i>UGT1A1</i>, and 2628 cases and 1744 controls for <i>ABCG8</i>. Comprehensive Meta-Analysis 3.0 software was used, applying fixed/random-effects models based on heterogeneity (<i>I</i><sup>2</sup> &gt; 50%, <i>p</i> &lt; 0.1). Bioinformatics tools evaluated nsSNP deleteriousness and protein stability.</p> Results <p>The <i>UGT1A1 rs6742078</i> variant was significantly associated with GSD (OR 1.119, 95% CI 1.017–1.232, <i>p</i> = 0.022). For <i>ABCG8 rs11887534</i>, the association was stronger (OR 2.573, 95% CI 1.988–3.329, <i>p</i> &lt; 0.001). Bioinformatic analyses predicted both <i>UGT1A1</i> rs72551341 and <i>ABCG8 rs11887534</i> nsSNPs as deleterious, leading to reduced protein stability and likely phenotypic consequences.</p> Conclusion <p>The meta-analysis confirms significant associations of <i>UGT1A1 rs6742078</i> and <i>ABCG8 rs11887534</i> polymorphisms with GSD, implicating glucuronidation and cholesterol transport pathways in disease etiology. Future studies should focus on functional analysis of these polymorphisms to enhance understanding of genetic predisposition to GSD and inform preventive strategies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A study on UGT1A1 and ABCG8 gene polymorphism: meta-analysis and bioinformatics approach in the etiology of gallstone disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月18日

查看全文
  • K. K. Shahaana Shireen,
  • S. Anu Aarthi,
  • D. Sylvia Nithila Illavarasi,
  • Sanjana Murali,
  • Nandini Krishnamurthy,
  • R. B. Devi Krishna,
  • A. Jagadesh,
  • Jayanthi Venkataraman,
  • Andrea Mary Francis

摘要

Background

Gallstone disease (GSD) is a prevalent chronic hepatobiliary condition characterized by impaired metabolism of cholesterol, bilirubin, and bile acids. Gallstones are categorized as cholesterol, pigment (black and brown), or mixed stones. Genetic predisposition accounts for approximately 25% of cases, with multiple variants influencing GSD susceptibility.

Objective

This study investigates the association of UGT1A1 (rs6742078) and ABCG8 (rs11887534) polymorphisms with GSD through a meta-analysis, bioinformatics assessment of non-synonymous SNPs (nsSNPs).

Methods

A systematic review of studies (UGT1A1 and ABCG8 from January 2000 to January 2020) was conducted using databases such as PubMed, Embase, Scopus, and Web of Science. Meta-analyses pooled data from 6492 cases and 59,635 controls for UGT1A1, and 2628 cases and 1744 controls for ABCG8. Comprehensive Meta-Analysis 3.0 software was used, applying fixed/random-effects models based on heterogeneity (I2 > 50%, p < 0.1). Bioinformatics tools evaluated nsSNP deleteriousness and protein stability.

Results

The UGT1A1 rs6742078 variant was significantly associated with GSD (OR 1.119, 95% CI 1.017–1.232, p = 0.022). For ABCG8 rs11887534, the association was stronger (OR 2.573, 95% CI 1.988–3.329, p < 0.001). Bioinformatic analyses predicted both UGT1A1 rs72551341 and ABCG8 rs11887534 nsSNPs as deleterious, leading to reduced protein stability and likely phenotypic consequences.

Conclusion

The meta-analysis confirms significant associations of UGT1A1 rs6742078 and ABCG8 rs11887534 polymorphisms with GSD, implicating glucuronidation and cholesterol transport pathways in disease etiology. Future studies should focus on functional analysis of these polymorphisms to enhance understanding of genetic predisposition to GSD and inform preventive strategies.