Gene

Biology

Cirrhosis

Environmental health

Single-nucleotide polymorphism

Genetics

Alcoholic liver disease

Minor allele frequency

Allele frequency

Genotype

Population

Internal medicine

Hepatology

Odds ratio

Medicine

Gastroenterology

Allele

Case-control study

Genotype frequency

Hepatology International

Objective Alcoholic liver disease (ALD) is a chronic liver disorder caused by the consumption of large amounts of alcohol. Genome-wide association studies have recently confirmed that polymorphisms in PNPLA3 predispose individuals to ALD and have identified risk loci of MBOAT7 and TM6SF2 in persons of European descent. However, the association with alcoholic liver damage has not been evaluated thus far in a Han Chinese population. Methods We performed a large case-control multicenter study of 507 ALD patients and 645 ethnically matched healthy controls. Five SNPs were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry, and association analysis was performed using PLINK 1.07 software. Results The rs738409 in the PNPLA3 gene was found to be significantly associated with ALD in allele and genotype frequencies (p = 6.25 × 10−14 and p = 9.05 × 10−13). The frequencies of the risk allele G in rs738409 were notably higher in ALD compared to controls (odds ratio = 1.93, 95% confidence interval = 1.63–2.28). The current study showed that the genotype frequencies of three genetic models were also statistically significant (p = 1.07 × 10−13, p = 9.3 × 10−8, and p = 1.57 × 10−12). Additionally, the G-allele of rs738409 was associated with a variety of clinical manifestations such as elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), and mean corpuscular volume (MCV) in the patients with ALD. Conclusion In a Han Chinese population, the present study confirmed that PNPLA3 polymorphism rs738409 was more likely to influence the susceptibility to ALD. However, no statistically significant differences for the allele and genotype frequencies of rs626283, rs641738 in MBOAT7, rs10401969 in SUGP1 and rs58542926 in TM6SF2 were found between ALD patients and healthy controls.

Single-nucleotide rs738409 polymorphisms in the PNPLA3 gene are strongly associated with alcoholic liver disease in Han Chinese males