Freedman B I, Espeland M A, Heise E R, Evans J, Canzanello V J
Department of Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1053.
J Am Soc Nephrol. 1993 Feb;3(8):1467-73. doi: 10.1681/ASN.V381467.
Black patients with insulin-dependent diabetes mellitus are at increased risk for the development of diabetic nephropathy compared with white patients. To determine if genetic differences associated with the HLA system account for racial variation in insulin-dependent diabetes mellitus-induced nephropathy, serologically defined HLA phenotypes from renal transplant recipients and donors in the South-Eastern Organ Procurement Foundation database from 1982 to 1986 were analyzed. Renal transplant recipients (N = 1,531) with insulin-dependent diabetes mellitus-induced renal failure as the cause of ESRD (patients) were compared with 4,506 race-matched, nondiabetic cadaveric kidney donors (controls). Log-linear models were used to assess the relationship between insulin-dependent diabetes mellitus-induced renal failure and prevalence of each HLA phenotype. Bonferroni adjustments of P values were used to correct for multiple comparisons. A comparison of HLA frequencies in patients with insulin-dependent diabetes mellitus-induced renal failure demonstrated the presence of racial differences beyond those normally present between the black and white populations. Blacks, compared with whites, had increased frequencies of HLA-B62 (odds ratio [OR] black:white, 6.13:1.97; P < 0.02) and HLA-DR9 (OR black:white, 4.82:1.57; P < 0.008) and decreased frequencies of HLA-A1 (OR white:black, 1.56:0.8; P < 0.008) and HLA-DR3 (OR white:black, 4.9:2.82; P < 0.004). These results suggest that differences in HLA frequency may account, in part, for the observed racial variation in incidence of diabetic nephropathy. In addition, several antigens in positive and negative association with diabetic nephropathy were identified within each race.
与白人患者相比,胰岛素依赖型糖尿病黑人患者发生糖尿病肾病的风险更高。为了确定与HLA系统相关的基因差异是否导致胰岛素依赖型糖尿病诱发的肾病存在种族差异,我们分析了1982年至1986年东南器官采购基金会数据库中肾移植受者和供者血清学定义的HLA表型。将因胰岛素依赖型糖尿病导致肾衰竭而成为终末期肾病的肾移植受者(N = 1531例,患者)与4506例种族匹配的非糖尿病尸体肾供者(对照)进行比较。使用对数线性模型评估胰岛素依赖型糖尿病诱发的肾衰竭与每种HLA表型患病率之间的关系。使用P值的Bonferroni校正来校正多重比较。对胰岛素依赖型糖尿病诱发肾衰竭患者的HLA频率进行比较,结果显示存在种族差异,这种差异超出了黑人和白人正常存在的差异。与白人相比,黑人的HLA - B62频率增加(优势比[OR]黑人:白人,6.13:1.97;P < 0.02)和HLA - DR9频率增加(OR黑人:白人,4.82:1.57;P < 0.008),而HLA - A1频率降低(OR白人:黑人,1.56:0.8;P < 0.008)和HLA - DR3频率降低(OR白人:黑人,4.9:2.82;P < 0.004)。这些结果表明,HLA频率的差异可能部分解释了观察到的糖尿病肾病发病率的种族差异。此外,在每个种族中都发现了与糖尿病肾病呈正相关和负相关的几种抗原。