ACE2基因多态性与儿童原发性肾病综合征的相关性研究

Association between angiotensin-converting enzyme 2 gene polymorphisms and childhood primary nephrotic syndrome

摘要:

目的 血管紧张素转换酶2(ACE2)基因多态性与高血压病、糖尿病肾病等多种疾病相关,是否参与儿童原发性肾病综合征(PNS)的发病尚不明确,该研究探讨广东汉族儿童ACE2 基因A9570G 多态性与PNS 的相关性。方法 选取广东汉族PNS 患儿66 例为肾病组,健康体检者60 例为对照组,采用聚合酶链反应-限制性核酸内切酶片段长度多态性技术分析肾病组与对照组的ACE2 基因A9570G 基因型分布和等位基因频率。结果 在女性和男性,两组间等位基因频率及基因型分布差异均无统计学意义(P>0.05)。肾病组按糖皮质激素治疗反应分为激素敏感组和激素耐药组,亚组分析发现,在女性,激素敏感组GG 基因型频率低于激素耐药组(17% vs 45%,P<0.05),激素敏感组G 等位基因频率亦低于激素耐药组(31% vs 61%,P<0.05);在男性,激素敏感组G 基因型/G 等位基因频率低于激素耐药组(36% vs 64%,P<0.05)。结论 ACE2 基因A9570G 多态性与儿童PNS 的发生无明确关联,但可能与PNS 患儿对糖皮质激素治疗的反应有关,G 等位基因可能是儿童PNS 激素耐药的遗传易感因素。

Abstract:

Objective Angiotensin-converting enzyme 2 (ACE2) gene polymorphisms have been shown to be implicated in hypertension, diabetic nephropathy, and other diseases. However, it remains unclear whether ACE2 gene polymorphisms are involved in the development of primary nephrotic syndrome (PNS) in children. The aim of this study was to assess the association between A9570G polymorphisms of ACE2 gene and PNS in a group of Han children in Guangdong Province, China. Methods The genotype distribution and allele frequency of ACE2 gene A9570G in 66 children with PNS and 60 healthy subjects (control group) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Results Allele frequency and genotype distribution showed no significant difference between the PNS and control groups whether in female or in male children (P>0.05). The PNS group was classified into the glucocorticoid-sensitive and glucocorticoid-resistant subgroups according to glucocorticoid treatment response. Subgroup analysis revealed that in female children, the frequency of GG genotype was 17% in the glucocorticoidsensitive group vs 45% in the glucocorticoid-sensitive group (P=0.018); the frequency of G allele was 31% in the glucocorticoid-sensitive group vs 61% in the glucocorticoid-resistant group (P=0.023). In male children, the frequency of G genotype/G allele was 36% in the glucocorticoid-sensitive group vs 64% in the glucocorticoid-resistant group (P=0.017). Conclusions There is no clear association between ACE2 gene A9570G polymorphisms and childhood PNS, but ACE2 gene A9570G polymorphisms might be associated with glucocorticoid treatment response in children with PNS. The G allele might be a genetic susceptibility factor of glucocorticoid resistance in children with PNS.