Confirmation of a susceptibility locus for diabetic nephropathy on chromosome 3q23-q24 by association study in Russian type 1 diabetic patients

Abstract

Family-based studies and segregation analyses suggest that inherited factors play a significant role in susceptibility to diabetic nephropathy (DN). Moczulski et al. [Diabetes 47 (1998) 1164-1169] found a susceptibility locus for DN in type 1 diabetes covering a 20cM region on chromosome 3q, with a peak of linkage close to the angiotensin II type 1 receptor (AT1) gene. We examined eight polymorphic markers (D3S1512, D3S1550, D3S1557, D3S1744, D3S2326, D3S3599, D3S3694, and a (CA)(n) dinucleotide repeat polymorphism in the 3' flanking region of the AT1 gene) spanning about 6.2 megabases (Mb) in the region of maximal linkage with DN on chromosome 3q23-q24. The markers were used to genotype a total of 381 Russian type 1 diabetic subjects, 195 of whom had DN and 186 had no clinical nephropathy. Four of the markers tested, D3S1512, D3S1550, D3S2326, and D3S3599, showed an association with DN in type 1 diabetes mellitus. These markers are located within a 1.0Mb interval that starts about 4.4Mb centromeric to the AT1 gene. Thus, our results suggest the existence of the DN susceptibility locus previously described by Moczulski et al. on chromosome 3q.