GCK基因多态性与原发性肾病综合征糖皮质激素治疗相关SD的关联分析

Association between GCK Gene Polymorphism and Glucocorticoid Therapy Related SD in Primary Nephrotic Syndrome

目的调查分析GCK基因多态性与原发性肾病综合征患者糖皮质激素治疗的类固醇性糖尿病(steroid diabetes,SD)的关系。方法在2015年1月~2019年12月,连续招募148名糖皮质激素治疗的原发性肾病综合征患者,从受试者的血液样本中提取DNA,分析GCK基因区域的rs13306388、rs2971672和rs1799884位点与SD发生的关联性。结果所有受试者的SD总发生率为35.1%(52/148)。SD组受试者的年龄大于非SD组(P<0.001),并且使用糖皮质激素浓度/剂量更高(P<0.05)。所有SNP的基因型分布均为Hardy-Weinberg平衡(P>0.05)。在GCK多态性的等位基因频率中,仅rs 2971672*C等位基因与SD的发生显著相关(OR=0.37;95%CI=0.16~0.80;P=0.012)。在多元logistic回归分析中调整年龄后,GCK基因型的SNP rs1799884(共显性2模型:OR=3.63,95%CI=1.19~12.06,P=0.027;隐性模型:OR=3.78,95%CI=1.22~11.94,P=0.035)和SNP rs2971672(共显性1模型:OR=0.32,95%CI=0.13~0.75,P=0.009;显性模型:OR=0.29,95%CI=0.12~0.68,P=0.002)与SD的发生显著相关。结论GCK基因区域的rs2971672和rs1799884位点突变可能影响糖皮质激素治疗的原发性肾病综合征患者SD事件的发生。

Objective To investigate and analyze the relationship between GCK gene polymorphism and steroid diabetes(SD)in patients with primary nephrotic syndrome treated with glucocorticoid.Methods From January 2015 to December 2019,148 patients with primary urinary nephrotic syndrome were continuously recruited,and they received glucocorticoid-induced immunotherapy.DNA was extracted from the subjects'blood samples,and the association between rs13306388,rs2971672 and rs1799884 in the GCK gene region and SD was analyzed.Results The total incidence of SD in all subjects was 35.1%(52/148).The subjects in the SD group were older than those in the non-SD group(P<0.001),and the glucocorticoid concentration/dose was higher(P<0.05).The genotype distribution of all SNPs was Hardy-Weinberg equilibrium(P>0.05).Among the allele frequencies of GCK polymorphism,only the rs2971672*C allele was significantly correlated with the occurrence of SD(OR=0.37;95%CI=0.16 to 0.80;P=0.012).After adjusting for age in multiple logistic regression analysis,the SNP of GCK genotype rs1799884(codominant 2 model:OR=3.63,95%CI=1.19~12.06,P=0.027;recessive model:OR=3.78,95%CI=1.22~11.94,P=0.035)and SNP rs2971672(commonly dominant 1 model:OR=0.32,95%CI=0.13~0.75,P=0.009;dominant model:OR=0.29,95%CI=0.12~0.68,P=0.002)is significantly related to the occurrence of SD.Conclusion The mutations at rs2971672 and rs1799884 in the GCK gene region may affect the occurrence of SD events in primary nephrotic syndrome receiving glucocorticoid immunosuppressive therapy.