TY - JOUR
T1 - CD2AP is associated with end-stage renal disease in patients with type 1 diabetes
AU - Hyvönen, Mervi E.
AU - Ihalmo, Pekka
AU - Sandholm, Niina
AU - Stavarachi, Monica
AU - Forsblom, Carol
AU - McKnight, Amy Jayne
AU - Lajer, Maria
AU - Maestroni, Anna
AU - Lewis, Gareth
AU - Tarnow, Lise
AU - Maestroni, Silvia
AU - Zerbini, Gianpaolo
AU - Parving, Hans Henrik
AU - Maxwell, Alexander P.
AU - Groop, Per Henrik
AU - Lehtonen, Sanna
PY - 2013/12/1
Y1 - 2013/12/1
N2 - CD2-associated protein (CD2AP) is essential for podocyte function. CD2AP mutations have been found in patients with focal segmental glomerulosclerosis, a disease histologically resembling diabetic nephropathy and often progressing to end-stage renal disease (ESRD). We hypothesised that variations in the CD2AP gene may contribute to susceptibility to glomerular injury in diabetes and investigated if single-nucleotide polymorphisms (SNPs) in CD2AP are associated with diabetic nephropathy in patients with type 1 diabetes. The discovery cohort consisted of 2,251 Finnish patients with type 1 diabetes. SNPs were selected from the HapMap database to cover the CD2AP gene. The associations between genotyped SNPs and diabetic nephropathy or ESRD were analysed with the chi-squared test and logistic regression. Three SNPs were selected for replication in cohorts from Denmark, Italy, the United Kingdom and Ireland. None of the 15 successfully genotyped SNPs were associated with diabetic nephropathy when compared to patients with normal albumin excretion rate. However, when genotype frequencies in patients with ESRD were compared with all other patients, two CD2AP SNPs, rs9369717 and rs9349417, were found to be associated with ESRD. The meta-analysis of the original and two additional European cohorts resulted in significant p values <0.01 for these SNPs. A third SNP, rs6936632, was suggestively associated with ESRD in the Finnish patients and in the meta-analysis of four cohorts. CD2AP gene variants may contribute to susceptibility to ESRD in patients with type 1 diabetes.
AB - CD2-associated protein (CD2AP) is essential for podocyte function. CD2AP mutations have been found in patients with focal segmental glomerulosclerosis, a disease histologically resembling diabetic nephropathy and often progressing to end-stage renal disease (ESRD). We hypothesised that variations in the CD2AP gene may contribute to susceptibility to glomerular injury in diabetes and investigated if single-nucleotide polymorphisms (SNPs) in CD2AP are associated with diabetic nephropathy in patients with type 1 diabetes. The discovery cohort consisted of 2,251 Finnish patients with type 1 diabetes. SNPs were selected from the HapMap database to cover the CD2AP gene. The associations between genotyped SNPs and diabetic nephropathy or ESRD were analysed with the chi-squared test and logistic regression. Three SNPs were selected for replication in cohorts from Denmark, Italy, the United Kingdom and Ireland. None of the 15 successfully genotyped SNPs were associated with diabetic nephropathy when compared to patients with normal albumin excretion rate. However, when genotype frequencies in patients with ESRD were compared with all other patients, two CD2AP SNPs, rs9369717 and rs9349417, were found to be associated with ESRD. The meta-analysis of the original and two additional European cohorts resulted in significant p values <0.01 for these SNPs. A third SNP, rs6936632, was suggestively associated with ESRD in the Finnish patients and in the meta-analysis of four cohorts. CD2AP gene variants may contribute to susceptibility to ESRD in patients with type 1 diabetes.
KW - Diabetic nephropathy
KW - End-stage renal disease
KW - Genetics
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=84890560124&partnerID=8YFLogxK
U2 - 10.1007/s00592-013-0475-9
DO - 10.1007/s00592-013-0475-9
M3 - Article
C2 - 23681557
AN - SCOPUS:84890560124
VL - 50
SP - 887
EP - 897
JO - Acta Diabetologica
JF - Acta Diabetologica
SN - 0940-5429
IS - 6
ER -