Influence of genomic loci on measures of chronic kidney disease in hypertensive sibships

Genomewide linkage analyses were conducted of serum creatinine, estimated GFR (eGFR), and urine albumin-creatinine ratio WACR) in search of genetic susceptibility loci for chronic kidney disease in 1351 black (median age 63 yr, 70% women, 79% hypertensive) and 1022 white individuals (median age 61 yr, 56% women, 75% hypertensive) from sibships in which two or more members had essential hypertension diagnosed before age 60 yr. After adjustment for gender, age, diabetes, and use of angiotensin inhibitors, the logarithm-transformed measure of serum creatinine was heritable in both ethnic groups (0.45 in black individuals [P < 0.0011; 0.39 in white individuals [P < 0.0011), as was eGFR (0.52 in black individuals [P < 0.0011; 0.39 in white individuals [P < 0.0011). Log UACR was heritable in black individuals (0.30, P < 0.001) but not in white individuals (0.12; P = 0.059). In black individuals, the univariate maximum multipoint logarithm of odds scores (MLS) were observed on chromosome 7 for log serum creatinine (MLS = 3.65, at 43 cM from pter; P = 0.00002) and eGFR (MLS = 2.52, at 45 cM from pter; P = 0.00033) and for log UACR (MLS = 2.91, at 112 cM from pter; P = 0.00012). In white individuals, only one MLS for log serum creatinine and one for eGFR achieved the logarithm of odds score criterion for suggestive evidence of linkage (2:5 MLS < 3), both on chromosome 3 (at 11 and 209 cM, respectively); however, none did so for log LTACR. In black individuals, bivariate linkage analyses of log serum creatinine and pulse pressure (i.e., systolic-diastolic BP) provided suggestive evidence of a region on chromosome 5 with pleiotropic effects on both traits (MLS = 3.62, at 85 cM from pter; P = 0.00023). These findings support the utility of genetic linkage analyses for identification of novel risk factors that influence measures of chronic kidney disease, particularly among black individuals.