Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy.
OBJECTIVE
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
The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.
Savage
D A
DA
Nephrology Research Laboratory, Queen's University, Belfast, BT9 7AB, Northern Ireland, UK. d.savage@qub.ac.uk
Patterson
C C
CC
Deloukas
P
P
Whittaker
P
P
McKnight
A J
AJ
Morrison
J
J
Boulton
A J
AJ
Demaine
A G
AG
Marshall
S M
SM
Millward
B A
BA
Thomas
S M
SM
Viberti
G C
GC
Walker
J D
JD
Sadlier
D
D
Maxwell
A P
AP
Bain
S C
SC
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007494:Ireland; D007676:Kidney Failure, Chronic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom
D007328:Insulin
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