Additive Effects of the Risk Alleles of PNPLA3 and TM6SF2 on Non-alcoholic Fatty Liver Disease (NAFLD) in a Chinese Population.
Additive Effects of the Risk Alleles of PNPLA3 and TM6SF2 on Non-alcoholic Fatty Liver Disease (NAFLD) in a Chinese Population.
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PNPLA3 和 TM6SF2 风险等位基因对中国人群非酒精性脂肪肝 (NAFLD) 的累加效应。
DOI：
10.3389/fgene.2016.00140
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发表时间：
2016
影响因子：
3.7
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Wang X;Liu Z;Wang K;Wang Z;Sun X;Zhong L;Deng G;Song G;Sun B;Peng Z;Liu W
最近的全基因组关联研究发现，PNPLA 3、NCAN、GCKR、LYPLAL 1和TM 6SF 2中或附近的变异与多个种族的非酒精性脂肪肝（NAFLD）显著相关。关于它们对汉族人NAFLD的影响的研究仍然有限。在这项研究中，我们研究了这些变异与社区汉族人群中NAFLD的相关性，并进一步探讨了它们对NAFLD的潜在联合作用。在384名NAFLD患者和384名年龄和性别匹配的健康对照者中，对先前在全基因组分析中确定的与NAFLD相关的6个单核苷酸多态性（SNP）（PNPLA 3 rs738409、rs 2294918、NCAN rs 2228603、GCKR rs780094、LYPLAL 1 rs 12137855和TM 6SF 2 rs 58542926）进行基因分型。我们发现6个多态性中的2个，PNPLA 3 rs738409（OR = 1.52，95%CI：1.19-1.96; P = 0.00087）和TM 6SF 2 rs 58542926（OR = 2.11，95%CI：1.34-3.39; P = 0.0016）在校正年龄、性别和BMI的影响后与NAFLD独立相关。我们的分析进一步证实了PNPLA 3和TM 6SF 2的危险等位基因具有很强的加性效应，其危险等位基因数与NAFLD之间具有总体显著性（OR = 1.64，95%CI：1.34-2.01; P = 1.4 × 10-6）。NAFLD的OR以累加的方式增加，每增加一个危险等位基因，OR平均增加1.52。我们的研究结果证实PNPLA 3和TM 6SF 2变异是中国人群中NAFLD最显著的危险等位基因。因此，对这两种遗传风险因素进行基因分型可能有助于识别NAFLD风险最高的个体。
Recent genome-wide association studies have identified that variants in or near PNPLA3, NCAN, GCKR, LYPLAL1, and TM6SF2 are significantly associated with non-alcoholic fatty liver disease (NAFLD) in multiple ethnic groups. Studies on their impact on NAFLD in Han Chinese are still limited. In this study, we examined the relevance of these variants to NAFLD in a community-based Han Chinese population and further explored their potential joint effect on NAFLD. Six single nucleotide polymorphisms (SNPs) (PNPLA3 rs738409, rs2294918, NCAN rs2228603, GCKR rs780094, LYPLAL1 rs12137855, and TM6SF2 rs58542926) previously identified in genome-wide analyses, to be associated with NAFLD were genotyped in 384 NAFLD patients and 384 age- and gender-matched healthy controls. We found two out of the six polymorphisms, PNPLA3 rs738409 (OR = 1.52, 95%CI: 1.19–1.96; P = 0.00087) and TM6SF2 rs58542926 (OR = 2.11, 95%CI: 1.34–3.39; P = 0.0016) are independently associated with NAFLD after adjustment for the effects of age, gender, and BMI. Our analysis further demonstrated the strong additive effects of the risk alleles of PNPLA3 and TM6SF2 with an overall significance between the number of risk alleles and NAFLD (OR = 1.64, 95%CI: 1.34–2.01; P = 1.4 × 10-6). The OR for NAFLD increased in an additive manner, with an average increase in OR of 1.52 per additional risk allele. Our results confirmed that the PNPLA3 and TM6SF2 variants were the most significant risk alleles for NAFLD in Chinese population. Therefore, genotyping these two genetic risk factors may help identify individuals with the highest risk of NAFLD.