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目的探讨肾胺酶基因(RNLS)rs2576178变异与合并微量白蛋白尿的非胰岛素依赖型糖尿病(2型糖尿病)肾病患者高血压发病的关系。方法以上海地区225例(均为汉族)合并微量白蛋白尿的2型糖尿病肾病患者(DN组)和251例无糖尿病、无肾脏疾病的健康对照者(Cont组)作为研究对象,DN组又再分为合并高血压组[DN-HTN(+)组]169例和未合并高血压组[DN-HTN(-)]56例进行分析。采用Taqman分型方法,检测以上研究对象RNLS基因rs2576178位点的基因分型,比较两组间基因型频率、等位基因频率分布及临床变量间的差异。结果 DN组和Cont组rs2576178基因型频率分布符合Hardy-Weinberg平衡定律。与Cont组相比,DN组AA基因型和A等位基因频率显著降低(P<0.05);应用非条件Logistic回归分析对所有研究对象的性别、年龄、体质量指数(BMI)进行校正后,rs2576178 AA基因型仍与高血压显著相关,OR(95%CI)为0.48(0.28~0.81)。与DN-HTN(-)组相比,DN-HTN(+)组GG+GA基因型和G等位基因频率显著增加(P<0.05)。对DN组性别、发病年龄、BMI进行校正后,rs2576178 AA基因型亦与高血压显著相关,OR(95%CI)为0.37(0.17~0.79)。结论 RNLS基因rs2576178 AA基因型可能具有防止合并微量白蛋白尿的2型糖尿病肾病患者高血压发生的作用。
Objective To investigate the relationship between rs2576178 polymorphism of renal aminase gene (RNLS) and hypertension in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes mellitus) with microalbuminuria. Methods Totally 225 diabetic patients with type 2 diabetic nephropathy (DN) and 251 non-diabetic and non-diabetic healthy controls (cont) with microalbuminuria were enrolled in this study. DN patients 169 cases of DN-HTN (+) group and 56 cases of DN-HTN (-) without hypertension group were further divided into two groups. The genotypes of rs2576178 of RNLS gene were detected by Taqman typing method. The genotype frequency, allele frequency distribution and clinical variables were compared between the two groups. Results The frequency distribution of rs2576178 genotype in DN group and Cont group was in accordance with Hardy-Weinberg equilibrium law. The frequency of AA genotype and A allele in DN group was significantly lower than that in Cont group (P <0.05). After adjustment for gender, age and body mass index (BMI) of all subjects using non-conditional Logistic regression analysis, The rs2576178 AA genotype was still significantly associated with hypertension, OR (95% CI) was 0.48 (0.28-0.81). Compared with DN-HTN (-) group, the frequencies of GG + GA genotype and G allele in DN-HTN (+) group increased significantly (P <0.05). The rs2576178 AA genotype was also significantly associated with hypertension after adjusting for gender, age of onset, and BMI in the DN group, with an OR (95% CI) of 0.37 (0.17-0.79). Conclusion The rs2576178 AA genotype of RNLS gene may play an important role in preventing hypertension in type 2 diabetic nephropathy patients with microalbuminuria.