Department of Clinical Laboratory, The First Hospital of Jilin University, Jilin, 130021, China.
Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
Hepatol Int. 2018 Sep;12(5):429-437. doi: 10.1007/s12072-018-9889-3. Epub 2018 Aug 21.
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 and p = 9.05 × 10). 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, p = 9.3 × 10, and p = 1.57 × 10). 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.
酒精性肝病（ALD）是一种由大量饮酒引起的慢性肝病。全基因组关联研究最近证实，PNPLA3 基因的多态性使个体易患 ALD，并在欧洲血统人群中确定了 MBOAT7 和 TM6SF2 的风险位点。然而，迄今为止，在汉族人群中尚未评估与酒精性肝损伤的相关性。
我们进行了一项大型病例对照多中心研究，共纳入 507 例 ALD 患者和 645 名匹配的健康对照。使用基质辅助激光解吸/电离飞行时间质谱法对 5 个 SNP 进行基因分型，并使用 PLINK 1.07 软件进行关联分析。
在等位基因和基因型频率中，发现 PNPLA3 基因中的 rs738409 与 ALD 显著相关（p=6.25×10 和 p=9.05×10）。与对照组相比，rs738409 中的风险等位基因 G 在 ALD 中的频率明显更高（比值比=1.93，95%置信区间=1.63-2.28）。本研究还显示，三种遗传模型的基因型频率也具有统计学意义（p=1.07×10、p=9.3×10 和 p=1.57×10）。此外，rs738409 的 G 等位基因与 ALD 患者的多种临床表现相关，如丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、γ-谷氨酰转肽酶（GGT）和平均红细胞体积（MCV）升高。
在汉族人群中，本研究证实 PNPLA3 多态性 rs738409 更可能影响 ALD 的易感性。然而，在 ALD 患者和健康对照之间，未发现 MBOAT7 中的 rs626283 和 rs641738、SUGP1 中的 rs10401969 和 TM6SF2 中的 rs58542926 的等位基因和基因型频率存在统计学差异。
