Peroxisome proliferators-activated receptor γ2 Pro12Ala variant is associated with body mass index in non-alcoholic fatty liver disease patients

• Published in: Hepatology international Vol. 5; no. 1; pp. 575 - 580
• Main Authors: Gupta, A. C., Chaudhory, A. K., Sukriti, Pande, C., Sakhuja, P., Singh, Y., Basir, S. F., Sarin, S. K.
• Format: Journal Article
• Language: English
• Published: India Springer-Verlag 01-12-2010
• Subjects: Colorectal Surgery; Hepatology; Medicine; Medicine & Public Health; Original; Original Article; Surgery; Peroxisome proliferator-activated receptor γ (PPAR γ); Non-alcoholic fatty liver Disease (NAFLD); Body mass index (BMI)
• ISSN: 1936-0533; 1936-0541
• DOI: 10.1007/s12072-010-9225-z

Background
Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and commonly associated with insulin resistance and metabolic syndrome (MS). Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor abundantly expressed in adipocytes and plays a key role in the regulation of adipocyte differentiation, lipid and glucose homeostasis. Pro12Ala variant has been earlier associated with obesity, type 2 diabetes and MS.
Aim
The present study aimed to determine the genotype frequencies of the Pro12Ala variant in NAFLD patients and any further association with other phenotype in the patients.
Patients and methods
Ninety-eight NAFLD patients and 280 matched controls were genotyped for presence of the Pro12Ala variant. Genomic DNA was extracted and polymerase chain reaction–restriction fragment length polymorphism using
Bst
-UI was performed for the detection of C–G change at codon 12 position of PPAR γ2 gene. Genotype and allele frequencies were compared between patients and controls. The Hardy–Weinberg equilibrium was tested by comparing expected/observed genotype frequencies by
χ
2
test.
Results
The frequencies of Pro/Ala genotype were comparable between NAFLD patients and controls. In the controls, 213 (75.7%) were homozygous for the wild-type (Pro/Pro) genotype and 67 (23.9%) were heterozygous (Pro/Ala). In NAFLD patients, genotypic distribution of wild type, heterozygous and homozygous were 63 (64.3%), 34 (34.7%) and 1 (1%), respectively. Heterozygous genotype was found to be significantly higher in the patients (
P
 = 0.01)
.
We also analyzed related phenotypic association of the patients with Pro12Ala genotype. We observed that the Pro12Ala (heterozygous) genotype was significantly higher in the patients who had body mass index >25 kg/m
2
(
P
 = 0.025).
Conclusions
Pro12Ala variation of the PPAR γ2 gene is associated with NAFLD and might play a role in the pathogenesis of NAFLD.