SREBP-2 1784 G/C genotype is associated with non-alcoholic fatty liver disease in north Indians

Article type: Research Article

Authors: Bhatt, Surya Prakash^{; ; ; ;} | Nigam, Priyanka^; | Misra, Anoop^; | Guleria, Randeep | Luthra, Kalpana | Vaidya, M. | Jain, S.K. | Pasha, M.A. Qadar

Affiliations: Department of Biochemistry, New Delhi, India | Department of Medicine, All India Institute of Medical Sciences, New Delhi, India | National Diabetes, Obesity, and Cholesterol Foundation, Diabetes Foundation (India), New Delhi, India | Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Aruna Asaf Ali Marg, Vasant Kunj, New Delhi, India | Department of Food and Nutrition. Govt. M.H. College of Home science and Science for woman, Jabalpur, India | Department of Biotechnology, Jamia Hamdard, New Delhi, India | Institute of Genomics and Integrative Biology, Delhi, India

Note: [] Address for correspondence: Anoop Misra, Director and Head, Fortis C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, Aruna Asaf Ali Marg, Vasant Kunj, New Delhi 110070, India. Tel.: +91 11 4277 6222 (Ext: 5029); Fax: +91 11 4277 6221; E-mail: anoopmisra@metabolicresearchindia.com

Abstract: Background: Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately investigated. This study aims to determine the association of the 1784G>C polymorphism in the SREBP-2 gene with NAFLD in Asian Indians in north India. Methods: In this study, (n=335); 162 obese with NAFLD, 91 obese without NAFLD and 82 non-obese without NAFLD subjects were recruited. Abdominal ultrasound, clinical profile, anthropometry, metabolic profile, serum levels of alanine aminotransferase, aspartate aminotransferase, fasting insulin and high sensitivity C-reactive protein (hs-CRP) were analysed. Polymerase chain reaction and restriction fragment length polymorphism were used to identify individual genotypes, and the association of this polymorphism with clinical and biochemical parameters was assessed. Results: The observed frequency of G allele was 0.73 and C allele was 0.27. Frequency of C/C genotype was higher in NAFLD as compared to obese and non-obese subjects (p=0.003). In NAFLD subjects 57.4% were G/G homozygous, 31.5% G/C heterozygous and 11.1% were C/C homozygous. The SREBP-2 genotype frequencies deviated from the Hardy Weinberg Equilibrium (X^{2}=6.39, p =0.0114). Mean values of TG (p = 0.002), TC (p =0.002), ALT (p =0.04) and AST (p =0.03) levels were significantly higher in NAFLD subjects with G/C genotype as compared to G/G genotypes in obese and non-obese groups. Fasting insulin (p =0.03), HOMA (p =0.009) and hs-CRP levels were significantly higher in NAFLD subjects with G/C genotype as compared to obese and non obese subjects with G/G genotypes. Conclusion: In this study, conducted for the first time in Asian Indians, SREBP-2 1784 G>C genotype was associated with NAFLD.

Keywords: Sterol regulatory element binding protein-2, Non-alcoholic fatty liver disease, Asian Indians, Alanine transaminase

DOI: 10.3233/DMA-2011-0852

Journal: Disease Markers, vol. 31, no. 6, pp. 371-377, 2011