吸烟和β3-肾上腺素能受体基因Trp64Arg、锰超氧化物歧化酶9Ala/Val基因多态性与非酒精性脂肪性肝病的相关性
Correlation of cigarette smoking and the polymorphisms of β3-adrenergic receptor gene Trp64Arg, MnSOD9Ala/Val genes with nonalcoholic fatty liver disease

摘要：目的 探讨吸烟和β3-肾上腺素能受体(β3-AR))基因Trp64Arg、锰超氧化物歧化酶9Ala/Val(MnSOD9Ala/Val)基因多态性与非酒精性脂肪性肝病(NAFLD)发病之间的关系。方法 采用病例-对照研究的方法，以720例NAFLD患者及720例健康对照者的外周血白细胞为样本，采用聚合酶链反应(PCR)技术分析β3-AR基因Trp64Arg和MnSOD9Ala/Val基因多态性。结果 β3-AR基因Trp64Arg (A/A)基因型和MnSOD9Ala/Val (V/V)基因型频率分布分别为39.4%、71.7%(病例组)和21.1%、43.3%(对照组)，差异有统计学意义(P<0.01；P<0.01)。Trp64Arg(A/A)基因型者患NAFLD的风险显著增加(OR=2.434，95% CI=1.816～4.075)。MnSOD9Ala/Val(V/V)基因型者患NAFLD的风险也显著增加(OR=3.308，95% CI=1.913～4.509)。基因突变的协同分析发现，Trp64Arg(A/A)/MnSOD9Ala/Val(V/V)基因型者在NAFLD组和对照组中的分布频率分别为32.8%和6.5%，差异有统计学意义(P<0.01)。Trp64Arg(A/A)/MnSOD9Ala/Val(V/V)基因型者患NAFLD的风险显著增加(OR=9.753，95% CI=4.292～12.426)。病例组的吸烟率显著高于对照组(OR=2.623，95% CI=1.425～4.957)，Trp64Arg(A/A)/MnSOD9Ala/Val(V/V)基因型与吸烟有协同作用(OR=33.764，95% CI=18.907～61.582)。结论 Trp64Arg (A/A)/MnSOD9Ala/Val(V/V)基因型和吸烟是NAFLD的易患因素，三者的联合在NAFLD的发生中起着协同的作用。
ABSTRACT: Objective To investigate the correlation of cigarette smoking and the combination of polymorphisms of β3-adrenergic receptor (β3-AR) gene Trp64Arg and manganese superoxide dismutase9Ala/Val (MnSOD9Ala/Val) genes with nonalcoholic fatty liver disease (NAFLD). Methods The genetic polymorphisms of β3-AR gene Trp64Arg and MnSOD9Ala/Val were analyzed by polymorphism-polymerase chain reaction (PCR) technique in peripheral blood leukocytes of 720 NAFLD patients and 720 healthy persons. Results The frequency of β3-AR gene Trp64Arg (A/A) and MnSOD9Ala/Val (V/V) was 39.4% and 71.7% in NAFLD patients and 21.1% and 43.3% in healthy controls, respectively. Statistical tests showed significant differences in the frequency between the two groups (P<0.01). The risk of NAFLD in patients carrying Trp64Arg(A/A) was significantly higher than that in the controls (OR=2.434, 95% CI=1.816-4.075). The individuals carrying MnSOD9Ala/Val (V/V) had a higher risk of NAFLD (OR=3.308, 95% CI=1.913-4.509). Combined analysis of the polymorphisms showed that the percentage of Trp64Arg (A/A)/MnSOD9Ala/Val (V/V) in NAFLD and control groups was 32.8% and 6.5%, respectively (P<0.01). The patients carrying Trp64Arg(A/A)/ MnSOD9Ala/Val (V/V) had a higher risk of NAFLD (OR=9.753, 95% CI= 4.292-12.426). The smoking rate of the case group was significantly higher than that in the control group (OR=2.623, 95% CI=1.425-4.957, P<0.01), and statistic analysis suggested an interaction between cigarette smoking and Trp64Arg(A/A)/MnSOD9Ala/Val(V/V) which increased the risk of NAFLD (OR=33.764, 95% CI=18.907-61.582). Conclusion Trp64Arg(A/A), MnSOD9Ala/Val (V/V) and cigarette smoking are the risk factors for NAFLD, and they can play a synergetic role in NAFLD