ESPE Abstracts (2018) 89 P-P1-094

ESPE2018 Poster Presentations Fat, Metabolism and Obesity P1 (42 abstracts)

Association of Single Nucleotide Polymorphisms in TNFA, PNPLA3, ADIPOQ and APOC3 Genes with Obesity and Non-Alcoholic Fatty Liver Disease in North Indian Adolescents

Vandana Jain , Anil Kumar , Manisha Jana & Mani Kalaivani

All India Institute of Medical Sciences, New Delhi, India

Background: Polymorphisms in several genes may be associated with a higher risk of obesity and non-alcoholic fatty liver disease (NAFLD).

Objective: To examine the association of single nucleotide polymorphisms (SNPs) −238G>A, −1031 T>C and −863 C>A of Tumor Necrosis Factor-α (TNFA) gene; rs738409 C>G of patatin-like phospholipase domain containing 3 (PNPLA3) gene; +276 G>T and +45 T>G of Adiponectin (ADIPOQ) gene and 455 T>C and 482 C>T of apolipoprotein C3 (APOC3) gene with obesity and NAFLD in north Indian adolescents.

Methods: In this case control study, 214 overweight/ obese adolescents aged 10 to 16 years and 86 healthy lean adults were enrolled. Ultrasonography was used to diagnose NAFLD and grade its severity. Body mass index, waist circumference, fasting plasma glucose, AST, ALT, and lipids were measured in the adolescents and controls; and serum insulin, adiponectin, apolipoprotein C3 and tumor necrosis factor-α (TNF-α) only in the adolescents. Genotyping was done for −238 G>A, −1031 T>C and −863 C>A of TNFA; rs738409 C>G of PNPLA3;+276 G>T and +45 T>G of ADIPOQ; and 455 T>C and 482 C>T of APOC3 genes. The frequency of hetero- and homozygous variant genotypes of the SNPs were compared among the overweight/ obese adolescents as a whole, and among the subgroups without NAFLD, with mild NAFLD and with moderate or severe NAFLD, with the lean adult controls. Odds ratios (OR, and 95% CI) for various genotypes in subjects in comparison to controls was calculated using multinomial logistic regression.

Results: NAFLD was present in 62.5% of the subjects, with the disease being mild, moderate and severe in 40.4, 18.8, and 3.3%, respectively. Variant (i.e., heterozygous and homozygous combined) genotypes of SNPs −1031 T>C and −863 C>A of TNFA gene were associated with overweight/obesity with OR of 2.47 (1.46–4.18) and 2.52 (1.45–4.35), respectively. Wild genotype of +276 G>T of ADIPOQ gene was associated with overweight/ obesity with OR of 2.58 (1.40-4.75). The SNP 455 T>C of APOC3 was associated with overweight/obesity with OR of 2.00 (1.11–3.61). The SNPs 455 T>C of APOC3 and rs738409 C>G of PNPLA3 were associated with moderate or severe NAFLD with OR of 5.04 (1.62–15.67) and 2.39 (1.09–5.28), respectively.

Conclusions: The study provides useful insight into the contributory role of genetic polymorphisms in the pathogenesis of predominantly lifestyle related conditions of obesity and NAFLD.

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