College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, 266003, China.
Department of Gastroenterology, Qingdao Municipal Hospital Group, Qingdao, 266011, China.
Lipids Health Dis. 2019 Feb 9;18(1):45. doi: 10.1186/s12944-019-0992-9.
PNPLA3 I148M variant and TM6SF2 E167K variant are recognized as the major genetic modifiers of nonalcoholic fatty liver disease (NAFLD). The present study sought to evaluate the potential additive effect of the two variants on the risk of NAFLD in Qingdao Han Population, China.
We genotyped PNPLA3 I148M variant and TM6SF2 E167K variant in a cohort of 512 unrelated NAFLD patients and 451 healthy controls by sequencing and polymerase chain reaction analysis. In addition, serum lipid profiles and liver enzymes were determined by standard clinical laboratory methods.
The minor allele frequencies were 45.48% for PNPLA3 148 locus G allele and 6.69% for TM6SF2 167 locus T allele. The PNPLA3 I148M variant was significantly associated with the risk of NAFLD in an additive model (CG, OR = 2.092, 95% CI: 1.551-2.820, P = 0.000; GG, OR = 4.566, 95% CI: 3.141-6.638, P = 0.000, respectively). And, our data suggested a strong link between the TM6SF2 E167K variant and the risk of NAFLD in a dominant model (CT + TT, OR = 2.327, 95% CI: 1.542-3.513, P = 0.000). In addition, the increasing of the number of risk alleles were associated with the risk of NAFLD (1 risk allele, OR = 1.687, P = 0.001; 2 risk alleles, OR = 4.326, P = 0.000; 3 risk alleles, OR = 6.018, P = 0.027, respectively).
Combining the I148M and E167K variants in a manner of an additive effect could improve risk prediction for NAFLD in a Qingdao Han Population cohort.
Chinese Clinical Trial Register.gov : ChiCTR1800015426.
PNPLA3 I148M 变体和 TM6SF2 E167K 变体被认为是影响非酒精性脂肪性肝病 (NAFLD) 的主要遗传修饰因子。本研究旨在评估这两种变体在中国青岛汉族人群中对 NAFLD 风险的潜在累加效应。
通过测序和聚合酶链反应分析，我们对 512 例无关联的 NAFLD 患者和 451 例健康对照者的 PNPLA3 I148M 变体和 TM6SF2 E167K 变体进行了基因分型。此外，通过标准临床实验室方法测定了血清脂质谱和肝酶。
PNPLA3 148 位 G 等位基因的次要等位基因频率为 45.48%，TM6SF2 167 位 T 等位基因的频率为 6.69%。在加性模型中，PNPLA3 I148M 变体与 NAFLD 风险显著相关（CG，OR=2.092，95%CI：1.551-2.820，P=0.000；GG，OR=4.566，95%CI：3.141-6.638，P=0.000）。此外，我们的数据表明，TM6SF2 E167K 变体与显性模型中的 NAFLD 风险之间存在很强的关联（CT+TT，OR=2.327，95%CI：1.542-3.513，P=0.000）。此外，风险等位基因数的增加与 NAFLD 风险相关（1 个风险等位基因，OR=1.687，P=0.001；2 个风险等位基因，OR=4.326，P=0.000；3 个风险等位基因，OR=6.018，P=0.027）。
以加性效应的方式结合 I148M 和 E167K 变体可以提高青岛汉族人群 NAFLD 的风险预测。
中国临床试验注册中心：ChiCTR1800015426。
