PNPLA3 rs1010023 Predisposes Chronic Hepatitis B to Hepatic Steatosis but Improves Insulin Resistance and Glucose Metabolism.
PNPLA3 rs1010023 Predisposes Chronic Hepatitis B to Hepatic Steatosis but Improves Insulin Resistance and Glucose Metabolism.
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PNPLA3 rs1010023 使慢性乙型肝炎易发生肝脂肪变性，但改善胰岛素抵抗和葡萄糖代谢
DOI：
10.1155/2017/4740124
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发表时间：
2017
影响因子：
4.3
通讯作者：
Fan JG
中科院分区：
文献类型：
--
作者：
Pan Q;Chen MM;Zhang RN;Wang YQ;Zheng RD;Mi YQ;Liu WB;Shen F;Su Q;Fan JG
PNPLA3基因多态性是正常人群肝脏脂肪变性的遗传基础，并导致糖代谢紊乱。它是否是慢性乙肝患者肝脏脂肪变性和葡萄糖稳态的基础仍不确定。在这里，我们研究了经肝活检证实的慢性乙型肝炎合并肝脂肪变性(CHB+HS组，n=52)或无肝脂肪变性(CHB组，n=47)和非CHB合并肝脂肪变性(HS组，n=37)或无肝脂肪变性(正常组，n=45)的PNPLA3基因多态性。与TT型相比，PNPLA3rs1010023的C等位基因(CC和TC)与年龄、性别和体重指数无关地增加了慢性乙型肝炎患者发生肝脏脂肪变性的风险(优势比(OR) = 为1.768，95%可信区间(CI)为1.027~3.105；P=0.045)。在CHB+HS组中，PNPLA3rs1010023的CC和TC基因型与稳态模型评估指数(HOMA-IR)的显著改善相关，与它们在肝脏脂肪变性中的作用相反。C等位基因位于PNPLA3rs1010023的CHB+HS患者空腹血糖水平降低(CC/TC比TT：4.81 ± 0.92 /L比5.86 ± 2.11 /L，P=0.02)。这些发现表明，PNPLA3 rs1010023可能使慢性乙肝患者容易发生肝脏脂肪变性，但通过减轻胰岛素抵抗来保护他们免受葡萄糖调节失调的影响。
PNPLA3 polymorphisms serve as the genetic basis of hepatic steatosis in normal population and lead to dysregulated glucose metabolism. Whether it underlies the hepatic steatosis and glucose homeostasis in chronic hepatitis B patients remains uncertain. Here, we investigated the PNPLA3 polymorphisms in biopsy-proven chronic hepatitis B patients with (CHB+HS group, n = 52) or without hepatic steatosis (CHB group, n = 47) and non-CHB subjects with (HS group, n = 37) or without hepatic steatosis (normal group, n = 45). When compared to the TT genotype, C-allele at PNPLA3 rs1010023 (CC and TC genotypes) conferred higher risk to hepatic steatosis in chronic hepatitis B patients (odds ratio (OR) = 1.768, 95% confidence interval (CI): 1.027–3.105; P = 0.045) independent of age, gender, and body mass index. In contrast to their role in hepatic steatosis, CC and TC genotypes of PNPLA3 rs1010023 were correlated to significant improvement of homeostasis model assessment index (HOMA-IR) as compared to TT genotype in the CHB+HS group. Downregulated fasting blood glucose also characterized the CHB+HS patients with C-allele at PNPLA3 rs1010023 (CC/TC versus TT: 4.81 ± 0.92 mmol/L versus 5.86 ± 2.11 mmol/L, P = 0.02). These findings suggest that PNPLA3 rs1010023 may predispose chronic hepatitis B patients to hepatic steatosis but protects them from glucose dysregulation by attenuating insulin resistance.