Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Gene. 2020 Jun 5;742:144585. doi: 10.1016/j.gene.2020.144585. Epub 2020 Mar 13.
The association between rs738409 (C>G, I148M) with patatin-like phospholipase domain-containing 3 (PNPLA3) gene and the risk of hepatocellular carcinoma (HCC) was controversial in different ethnic populations. Our study aimed to explore the effect of PNPLA3 rs738409 on the risk of HCC and persistent infection of Hepatitis B virus (HBV) in a Chinese HBV-related population, and further evaluate its role in HCC risk among Asians. First, we performed a case-control study by recruiting 786 HBV-related HCC cases, 695 HBV persistent carriers and 719 HBV natural clearance subjects. PNPLA3 rs738409 was genotyped by MassARRAY platform. Second, we conducted a systematic review and meta-analysis on Asians to further validate our results. Our case-control study demonstrated that PNPLA3 rs738409 was not associated with HCC risk or persistent HBV infection (All P > 0.05). The subsequent meta-analysis included 13 Asian studies with 9,802 subjects. Results showed that PNPLA3 rs738409 might increase HCC risk among healthy subjects (pooled odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.11-1.95), but it had no influence on the development of HCC among HBV-related subjects (pooled OR = 1.07, 95%CI = 0.89-1.30). Our case-control study highlights that PNPLA3 rs738409 is probably not associated with the risk of HCC or persistent HBV infection in a Chinese HBV-related population. Besides, our systematic review and meta-analysis on Asians further suggest that PNPLA3 rs738409 may confer an increased risk of HCC among healthy people, but contribute little to the development of HCC among HBV-related subjects. Future studies are required to confirm these results.
rs738409（C>G，I148M）与 patatin-like phospholipase domain-containing 3（PNPLA3）基因之间的关联及其与肝细胞癌（HCC）的风险在不同种族人群中存在争议。我们的研究旨在探讨 PNPLA3 rs738409 在中国乙型肝炎病毒（HBV）相关人群中对 HCC 风险和 HBV 持续感染的影响，并进一步评估其在亚洲人群中 HCC 风险中的作用。首先，我们通过招募 786 例 HBV 相关 HCC 病例、695 例 HBV 持续携带者和 719 例 HBV 自然清除者进行病例对照研究。使用 MassARRAY 平台对 PNPLA3 rs738409 进行基因分型。其次，我们对亚洲人群进行了系统评价和荟萃分析，以进一步验证我们的结果。我们的病例对照研究表明，PNPLA3 rs738409 与 HCC 风险或 HBV 持续感染无关（均 P>0.05）。随后的荟萃分析纳入了 13 项包含 9802 例受试者的亚洲研究。结果表明，PNPLA3 rs738409 可能会增加健康人群中 HCC 的风险（汇总优势比 [OR] = 1.47，95%置信区间 [CI] = 1.11-1.95），但对 HBV 相关人群中 HCC 的发生无影响（汇总 OR = 1.07，95%CI = 0.89-1.30）。我们的病例对照研究强调，PNPLA3 rs738409 可能与中国 HBV 相关人群中 HCC 的风险或 HBV 持续感染无关。此外，我们对亚洲人群的系统评价和荟萃分析进一步表明，PNPLA3 rs738409 可能会增加健康人群中 HCC 的风险，但对 HBV 相关人群中 HCC 的发生贡献不大。需要进一步的研究来证实这些结果。
