HNF1A、HNF1B、C/EBPA和ZHX2基因多态性与血清AFP水平相关性研究

Correlation between HNF1A, HNF1B, C/EBPA and ZHX2 Gene Polymorphisms and Serum AFP Levels

目的探讨HNF1A-rs1169288(A/C)和rs2464196(G/A)、HNF1B-rs4430796(A/G)、C/EBPA-rs34529039(C/A)和ZHX2-rs7844465(G/T)基因多态性与中国健康成人血清甲胎蛋白(AFP)水平的相关性。方法纳入笔者医院2017年1~11月1010例年龄在25~65岁的汉族健康体检人员,采用等位基因特异性引物结合荧光定量PCR的方法(ARMS-TaqMan法)进行等位基因分型检测。血清AFP采用美国雅培公司i2000免疫分析仪测定。结果1010例研究对象的rs2464196最小等位基因A的频率为0.479。AFP水平在rs2464196-AA型(247例)最低,为3.60±1.59ng/ml,AG型(473例)为3.92±1.78ng/ml,GG型(290例)最高,为4.21±2.10ng/ml(P<0.001)。线性回归分析显示在控制影响AFP水平的各临床指标后,rs2464196基因多态性仍与血清AFP水平显著相关(P=0.000)。而HNF1A-rs1169288,HNF1B-rs4430796,C/EBPA-rs34529039和ZHX2-rs7844465多态性与血清AFP水平无显著相关。结论在表观健康成年人中,HNF1A-rs2464196A等位基因与血清AFP水平降低具有显著相关性,该发现为血清AFP水平变化提供了新的遗传决定因子。

Objective To investigate the correlation between HNF1A-rs1169288 (A/C) and rs2464196 (G/A),HNF1B-rs4430796 (A/G),C/EBPA-rs34529039 (C/A) and ZHX2-rs7844465 (G/T) gene polymorphisms and serum AFP levels in Chinese healthy adults.Methods From January 2017 to November 2017,a total of 1010 non-related Han-Chinese healthy adults aged 25 to 65 years were enrolled.Single nucleotide polymorphisms (SNPs) were genotyped by the amplification refractory mutation system (ARMS) combined with TaqMan probe in a real time PCR.The serum AFP concentrations were measured by Architect i2000 immunochemistry analyzer.Results The minimum allele frequency of rs2464196-A was 0.479.Serum AFP levels were the lowest in HNF1A-rs2464196 AA (247 cases,3.60±1.59ng/ml),middle level in AG (473 cases,3.92±1.78ng/ml),and the highest in GG (290 cases,4.21±2.10ng/ml)( P =0.000).Linear regression analysis showed that HNF1A-rs2464196 polymorphism was still significantly associated with serum AFP level even after control of clinical covariates known to influence AFP level ( P =0.000).While the HNF1A-rs1169288,HNF1B-rs4430796,C/EBPA-rs34529039 and ZHX2-rs7844465 polymorphisms had no significant associations with serum AFP level.Conclusion The HNF1A-rs2464196 A allele was significantly associated with decreased serum AFP levels in Chinese-Han healthy adults.This finding provided a new insight into genetic determinants of AFP.