新疆维吾尔族IgA肾病血管紧张素转换酶、血管紧张素原和内皮型一氧化氮合酶基因多态性研究

Polymorphisms of angiotensin converting enzyme,angiotensinogen and endothelial nitric oxide synthase gene in IgA nephropathy in Xinjiang Uygur

目的探讨血管紧张素转换酶(angiotensin converting enzyme,ACE)、血管紧张素原(angiotensinogen,AGT)、内皮型一氧化氮合酶(endothelial nitricoxide synthase,eNOS)基因多态性与新疆维吾尔族IgA肾病相关性。方法选择2011年6月至2015年5月在新疆维吾尔自治区人民医院经肾脏病理和生化检测[血白蛋白(serum albumin,Alb)、血肌酐、24 h尿蛋白定量等实验室检查]等综合确诊的45例IgA肾病患者为IgA肾病组;另选择健康体检者45例为健康对照。选取直接测序方法检测ACE I/D、AGT M235T、eNOS G894T位点单核苷酸多态性(single nucleotide polymorphism,SNP)。结果 ACE I/D和AGT M235T的基因型和等位基因频率在2组之间分布差异无统计学意义(P>0.05)。IgA肾病组eNOS GG基因型和G等位基因的频率(62.2%,75.6%)高于健康对照组(26.7%,50.0%),差异均有统计学意义(χ~2=11.520,P=0.001;χ~2=12.577,P<0.0001)。ACE DD基因型患者的血肌酐[178.00(101.99,204.24)μmol/L]明显高于ACEⅡ基因型的患者[78.27(64.23,112.78)μmol/L],2种基因型间差异有统计学意义(P=0.018)。AGT M235T、eNOS G894T各基因型间血肌酐差异无统计学意义(P>0.05)。ACE DD基因型患者的24 h尿蛋白定量[2.66(1.44,3.87)g]明显高于ACEⅡ基因型患者的[1.31(0.14,2.65)g],2组间差异有统计学意义(P=0.023);AGT M235T、eNOS G894T各基因型间24 h尿蛋白定量差异均无统计学意义(P>0.05);ACE I/D、AGT M235T和eNOS G894T各基因型间血尿差异均无统计学意义(P>0.05)。结论ACE/AGT与新疆维吾尔族IgA肾病患者的易感性无关,eNOS基因可能是新疆维吾尔族IgA肾病患者的一个易感因素,ACE基因DD基因型与新疆维吾尔族IgA肾病的进展相关。

Objective To investigate the correlation between single nucleotide polymorphism of angiotensin converting enzyme （ACE）, angiotensinogen （AGT） and endothelial nitric oxide synthase （eNOS） with IgA nephropathy. Methods A total of 90 Xinjiang Uygvr were enrolled, including 45 cases of IgA nephropathy and 45 healthy controls. Results The frequencies of genotype and allele distribution in ACE I/D and AGT M235T showed no significant difference （P〉0. 05） between IgA nephropathy and control groups. The frequencies of eNOS G894T GG genotype and G allele （62. 2% and 75.6%, respectively） in IgA nephropathy group were significantly higher than those in control group （χ^2 = 11. 520, P = 0. 001; χ^2 = 12. 577, P〈0. 0001, respectively）. The serum creatinine in ACE DD genotype [178.00 （101.99, 204. 24）μmol/L] was significantly higher than that of ACE Ⅱ genotype [78. 27 （64. 23, 112. 78） μmol/L] with the difference being statistically significant （P = 0. 018）. The association of AGT M235T/eNOS G894T genotypes and serum creatinine showed no statistically sig- nificant difference between the two groups （P〉0. 05）. 24-h proteinuria in ACE DD genotype E2. 66 （1.44, 3.87） g] was significantly higher than that of ACE genotype Ⅱ [1.31（0. 14, 2. 65） g]（P = 0. 023）, with no significant differences between AGT M235T and eNOS G894T gene （P〉0. 05）. Association of ACE I/D, AGT M235T and eNOS G894T genotypes and hematuria showed no statistically significant difference between the two groups （P〉0. 05）. Conclusions ACE I/D, and AGT M235T genes are irrelevant to the susceptibility of patients with IgA nephropathy in Xinjiang Uygur. eNOS gene may be a risk factor in patients with IgA nephropathy. DD genotype in ACE gene is associated with the progression of IgA nephropathy in Xinjiang Uygur.