Abstract
Introduction: There is growing evidence that genetic and environmental factors play an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). We investigated the association of single nucleotide polymorphism (SNP) rs738409 in PNPLA3 gene and TNF-α G238A polymorphism with the development and severity of NAFLD in an overweight and obese Egyptian population. Material and Methods: 100 overweight and obese patients with NAFLD and 30 control subjects were enrolled. All NAFLD patients underwent a confirmatory biopsy. Laboratory investigations included fasting plasma glucose, kidney and liver function tests, liver enzymes, lipid profile and hepatitis markers. Abdominal ultrasound was performed and all subjects were genotyped for (rs738409) PNPLA3 and (rs361525) TNF-α gene polymorphisms using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: The homozygous GG genotype of the PNPLA3 was most frequent among patients with NASH (26%) as compared to borderline NASH (20.5%) and simple steatosis (20%). Higher serum levels of transaminases were observed in NAFLD patients and controls who were carriers of the G allele of rs738409, but this was not statistically significant. Regarding the TNF-α G238A SNP; the frequency of the A allele was significantly higher in NAFLD patients (20%) compared to controls (5%) (p value = 0.006). The highest TNF G allele frequency was observed in the NASH group (88%) and this was statistically significant (p value = 0.009). Conclusion: Our study confirmed the association of the PNPLA3 (rs738409) and TNF-α promoter region G238A polymorphisms with susceptibility to NAFLD and its progression.
Highlights
There is growing evidence that genetic and environmental factors play an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD)
The first Genome-wide association (GWA) study identified the patain-like phospholipase domain containing3 (PNPLA3) gene polymorphism as a major genetic determinant for the predisposition to NAFLD in Hispanic, African American and European Americans populations according to liver fat content [5], which was subsequently confirmed in Europeans and Asians according to liver biopsy
In the present study we evaluated the clinical and metabolic parameters, the liver histology, and the presence of polymorphisms in the PNPLA3 gene and the tumor necrosis factor-α (TNF-α) promoter region (G-238A) in NAFLD patients and controls
Summary
There is growing evidence that genetic and environmental factors play an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). We investigated the association of single nucleotide polymorphism (SNP) rs738409 in PNPLA3 gene and TNF-α G238A polymorphism with the development and severity of NAFLD in an overweight and obese Egyptian population. The first Genome-wide association (GWA) study identified the PNPLA3 gene polymorphism as a major genetic determinant for the predisposition to NAFLD in Hispanic, African American and European Americans populations according to liver fat content [5], which was subsequently confirmed in Europeans and Asians according to liver biopsy. The association of PNPLA3 gene polymorphisms with fatty liver and triglyceride content, and with histological severity of NAFLD was shown in subsequent studies [7] [8]
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