A genome scan for diabetic nephropathy in African Americans.
BACKGROUND
There is substantial evidence for a genetic contribution to diabetic nephropathy susceptibility in the African American population, but little is known about location or identity of susceptibility genes.


METHODS
DNA samples were collected from 206 type 2 diabetes (T2DM) and end-stage renal disease (ESRD)/nephropathy-affected sib pairs from 166 African American families (355 affected individuals). A genome scan was performed and data analyzed using nonparametric linkage regression (NPLR) analysis and ordered subsets analysis (OSA) methods.


RESULTS
In initial NPLR analyses no logarithm of odds (LOD) scores >2.0 were observed. Four loci had LOD scores > or =1.0, with LOD = 1.43 at 29 cM on chromosome 7p the highest. NPLR analyses of multilocus interactions detected 6 loci (7p, 12p, 14q, 16p, 18q, and 21q) with LOD scores 1.15 to 1.63. NPLR analyses evaluating phenotypic interactions revealed multiple locations with evidence (P < 0.05) for interactions with age-at-onset of ESRD (9 loci), duration of diabetes before onset of ESRD (19 loci), and age-at-onset of diabetes (14 loci). Several loci identified by NPLR analyses were also identified using OSA. OSA revealed evidence for a nephropathy locus at 135 cM on chromosome 3 in an estimated 29% of the families (LOD = 4.55 in the optimal subset). Additional linkage evidence, LOD = 3.59, was observed on chromosome 7p (37% of the families, longer duration of diabetes prior to diagnosis of ESRD), and 18q (max. LOD = 3.72; 64% of the families, early diabetes diagnosis). The 7p linkage has been observed in a recent genome scan of African American type 2 diabetes.


CONCLUSIONS
This first genome scan of diabetic nephropathy in African Americans reveals evidence for susceptibility loci on chromosomes 3q, 7p, and 18q. The 7p locus may represent a type 2 diabetes susceptibility locus.
Department of Biochemistry, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA. dbowden@wfubmc.edu
Donald W
DW
Bowden
Carla J
CJ
Colicigno
Carl D
CD
Langefeld
Michèle M
MM
Sale
Adrienne
A
Williams
Pamela J
PJ
Anderson
Stephen S
SS
Rich
Barry I
BI
Freedman
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D017668:Age of Onset; D003928:Diabetic Nephropathies / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000235:genetics; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010641:Phenotype