Genetic Susceptibility to Chronic Liver Disease in Individuals from Pakistan

• Main Authors: Asad Mehmood Raja, Ester Ciociola, Imran Nazir Ahmad, Faisal Saud Dar, Syed Muhammad Saqlan Naqvi, Muhammad Moaeen-ud-Din, Ghazala Kaukab Raja, Stefano Romeo, Rosellina Margherita Mancina
• Format: Article
• Language: English
• Published: MDPI AG 2020-05-01
• Series: International Journal of Molecular Sciences
• Subjects: NAFLD; Asia; ADPN; adiponutrin; TMC4; LPIAT1
• Online Access: https://www.mdpi.com/1422-0067/21/10/3558
• ISSN: 1661-6596; 1422-0067

Chronic liver disease, with viral or non-viral etiology, is endemic in many countries and is a growing burden in Asia. Among the Asian countries, Pakistan has the highest prevalence of chronic liver disease. Despite this, the genetic susceptibility to chronic liver disease in this country has not been investigated. We performed a comprehensive analysis of the most robustly associated common genetic variants influencing chronic liver disease in a cohort of individuals from Pakistan. A total of 587 subjects with chronic liver disease and 68 healthy control individuals were genotyped for the <i>HSD17B13</i> rs7261356, <i>MBOAT7</i> rs641738, <i>GCKR</i> rs1260326, <i>PNPLA3</i> rs738409, <i>TM6SF2</i> rs58542926 and <i>PPP1R3B</i> rs4841132 variants. The variants distribution between case and control group and their association with chronic liver disease were tested by chi-square and binary logistic analysis, respectively. We report for the first time that <i>HSD17B13</i> variant results in a 50% reduced risk for chronic liver disease; while <i>MBOAT7; GCKR</i> and <i>PNPLA3</i> variants increase this risk by more than 35% in Pakistani individuals. Our genetic analysis extends the protective role of the <i>HSD17B13</i> variant against chronic liver disease and disease risk conferred by the <i>MBOAT7</i>; <i>GCKR</i> and <i>PNPLA3</i> variants in the Pakistani population.