PMID- 18773191
OWN - NLM
STAT- MEDLINE
DCOM- 20081118
LR  - 20211020
IS  - 0012-186X (Print)
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 51
IP  - 11
DP  - 2008 Nov
TI  - Genetic association analyses of non-synonymous single nucleotide polymorphisms in 
      diabetic nephropathy.
PG  - 1998-2002
LID - 10.1007/s00125-008-1142-5 [doi]
AB  - AIMS/HYPOTHESIS: Diabetic nephropathy, characterised by persistent proteinuria, 
      hypertension and progressive kidney failure, affects a subset of susceptible 
      individuals with diabetes. It is also a leading cause of end-stage renal disease 
      (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been 
      reported to contribute to genetic susceptibility in both monogenic disorders and 
      common complex diseases. The objective of this study was to investigate whether 
      nsSNPs are involved in susceptibility to diabetic nephropathy using a 
      case-control design. METHODS: White type 1 diabetic patients with (cases) and 
      without (controls) nephropathy from eight centres in the UK and Ireland were 
      genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray 
      assay. A chi (2) test for trend, stratified by centre, was used to assess 
      differences in genotype distribution between cases and controls. Genomic control 
      was used to adjust for possible inflation of test statistics, and the False 
      Discovery Rate method was used to account for multiple testing. RESULTS: We 
      assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 
      individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs 
      demonstrated a significant difference in genotype distribution between groups 
      before but not after correction for multiple testing. Furthermore, neither 
      subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without 
      ESRD) nor stratification by duration of diabetes revealed any significant 
      differences between groups. CONCLUSIONS/INTERPRETATION: The nsSNPs investigated 
      in this study do not appear to contribute significantly to the development of 
      diabetic nephropathy in patients with type 1 diabetes.
FAU - Savage, D A
AU  - Savage DA
AD  - Nephrology Research Laboratory, Queen's University, Belfast, BT9 7AB, Northern 
      Ireland, UK. d.savage@qub.ac.uk
FAU - Patterson, C C
AU  - Patterson CC
FAU - Deloukas, P
AU  - Deloukas P
FAU - Whittaker, P
AU  - Whittaker P
FAU - McKnight, A J
AU  - McKnight AJ
FAU - Morrison, J
AU  - Morrison J
FAU - Boulton, A J
AU  - Boulton AJ
FAU - Demaine, A G
AU  - Demaine AG
FAU - Marshall, S M
AU  - Marshall SM
FAU - Millward, B A
AU  - Millward BA
FAU - Thomas, S M
AU  - Thomas SM
FAU - Viberti, G C
AU  - Viberti GC
FAU - Walker, J D
AU  - Walker JD
FAU - Sadlier, D
AU  - Sadlier D
FAU - Maxwell, A P
AU  - Maxwell AP
FAU - Bain, S C
AU  - Bain SC
LA  - eng
GR  - 077011/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20080905
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Insulin)
SB  - IM
MH  - Adult
MH  - Diabetes Mellitus, Type 1/drug therapy/*genetics
MH  - Diabetic Nephropathies/*genetics
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Insulin/therapeutic use
MH  - Ireland
MH  - Kidney Failure, Chronic/genetics
MH  - *Polymorphism, Single Nucleotide
MH  - United Kingdom
PMC - PMC2687720
MID - UKMS4502
OID - NLM: UKMS4502
EDAT- 2008/09/06 09:00
MHDA- 2008/11/19 09:00
PMCR- 2009/05/28
CRDT- 2008/09/06 09:00
PHST- 2008/05/07 00:00 [received]
PHST- 2008/07/31 00:00 [accepted]
PHST- 2008/09/06 09:00 [pubmed]
PHST- 2008/11/19 09:00 [medline]
PHST- 2008/09/06 09:00 [entrez]
PHST- 2009/05/28 00:00 [pmc-release]
AID - 10.1007/s00125-008-1142-5 [doi]
PST - ppublish
SO  - Diabetologia. 2008 Nov;51(11):1998-2002. doi: 10.1007/s00125-008-1142-5. Epub 
      2008 Sep 5.