Surya Prakash Bhatt1, Anoop Misra2, Ravindra Mohan Pandey3. 1. Diabetes Foundation (India), Safdarjung Development Area, New Delhi, 110016, India; National Diabetes Obesity and Cholesterol Foundation (N-DOC), Safdarjung Development Area, New Delhi, 110016, India; Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India; Fortis C-DOC Center of Excellence for Diabetes, Metabolic Diseases, and Endocrinology, B-16, Chirag Enclave, New Delhi, India. 2. Diabetes Foundation (India), Safdarjung Development Area, New Delhi, 110016, India; National Diabetes Obesity and Cholesterol Foundation (N-DOC), Safdarjung Development Area, New Delhi, 110016, India; Fortis C-DOC Center of Excellence for Diabetes, Metabolic Diseases, and Endocrinology, B-16, Chirag Enclave, New Delhi, India. Electronic address: anoopmisra@gmail.com. 3. Biostatics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Abstract
BACKGROUND AND AIMS: Transcription factor 7 like 2 (TCF7L-2) polymorphism has been associated with adipocyte metabolism and insulin resistance. Genetic investigations of non-alcoholic fatty liver disease (NAFLD) with obesity, type 2 diabetes mellitus (T2DM) and atherosclerosis are unknown. This study was designed to investigate the association of rs7903146 (C/T) polymorphism of TCF7L-2 gene with non-alcoholic fatty liver disease (NAFLD) in Asian Indians. METHODS: In this case-control study 162 non-diabetic subjects with NAFLD and 173 body mass index (BMI)-matched controls without NAFLD were recruited. Abdominal ultrasound, clinical and biochemical investigations, fasting insulin levels and value of homeostasis model assessment of insulin resistance (HOMA-IR) was measured. Single nucleotide polymorphism rs7903146 (C/T) was genotyped by polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: The distribution of rs7903146 (C/T) alleles, the dominant model (CT + TT) and higher frequency (31%) of C/T genotype were significantly associated with NAFLD. C/T genotype of TCF7L2 gene was associated with significantly higher levels of BMI (p = 0.02), abdominal obesity (p < 0.05), fasting blood glucose (p = 0.05), hepatic transaminases (p < 0.05) and markers of insulin resistance (p < 0.05) in subjects with NAFLD. Using a multivariate analysis after adjusting for age and sex, TCF7L2 polymorphism was independently associated with presence of NAFLD [(OR: 3.234 (95% CI: 1.219-4.160, p = 0.002)]. CONCLUSION: TCF7L2 (C/T) gene was Independently associated with NAFLD in Asian Indians.
BACKGROUND AND AIMS: Transcription factor 7 like 2 (TCF7L-2) polymorphism has been associated with adipocyte metabolism and insulin resistance. Genetic investigations of non-alcoholic fatty liver disease (NAFLD) with obesity, type 2 diabetes mellitus (T2DM) and atherosclerosis are unknown. This study was designed to investigate the association of rs7903146 (C/T) polymorphism of TCF7L-2 gene with non-alcoholic fatty liver disease (NAFLD) in Asian Indians. METHODS: In this case-control study 162 non-diabetic subjects with NAFLD and 173 body mass index (BMI)-matched controls without NAFLD were recruited. Abdominal ultrasound, clinical and biochemical investigations, fasting insulin levels and value of homeostasis model assessment of insulin resistance (HOMA-IR) was measured. Single nucleotide polymorphism rs7903146 (C/T) was genotyped by polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: The distribution of rs7903146 (C/T) alleles, the dominant model (CT + TT) and higher frequency (31%) of C/T genotype were significantly associated with NAFLD. C/T genotype of TCF7L2 gene was associated with significantly higher levels of BMI (p = 0.02), abdominal obesity (p < 0.05), fasting blood glucose (p = 0.05), hepatic transaminases (p < 0.05) and markers of insulin resistance (p < 0.05) in subjects with NAFLD. Using a multivariate analysis after adjusting for age and sex, TCF7L2 polymorphism was independently associated with presence of NAFLD [(OR: 3.234 (95% CI: 1.219-4.160, p = 0.002)]. CONCLUSION:TCF7L2 (C/T) gene was Independently associated with NAFLD in Asian Indians.