Single-nucleotide rs738409 polymorphisms in the PNPLA3 gene are strongly associated with alcoholic liver disease in Han Chinese males
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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.
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.
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.
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.
KeywordsAlcoholic liver diseases Han Chinese Single-nucleotide polymorphism PNPLA3 MBOAT7 TM6SF2 SUGP1
Alcoholic liver disease
Genome-wide association studies
Erythrocyte mean corpuscular volume
We are most grateful to all our colleagues who contributed to the ALD study. We thank Chunlei Cao of the Beijing Institute of Genomics for help and suggestions in genotyping and data analysis.
YFZ and FNY conceived the project, conducted the experiment, statistical analysis, and drafting of manuscript; TSG and YLM collected the samples and provided valuable discussion; YZL and JH supervised the experiment, revised the paper, and performed statistical analysis; LBL, CXL, and SQ collected the samples and extracted genomic DNA.
Compliance with ethical standards
Conflict of interest
Yanfang Zhang, Tongsheng Guo, Funing Yang, Yuanli Mao, Liubing Li, Chenxi Liu, Qiang Sun, Yongzhe Li, and Jing Huang declare no conflict of interest.
The study followed the rules of the ethical committees of four participating centers.
All participants in this study gave informed consent prior to enrollment.
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