Nephrology Dialysis Transplantation, Vol 14, Issue 4 891-894, Copyright © 1999 by Oxford University Press
D Savage, S Feeney, D Fogarty and A Maxwell
Background. It has recently been reported that the
risk of developing nephropathy in patients with insulin dependent (type 1)
diabetes mellitus is strongly associated with synergism between poor
glycaemic control and carriage of the hypertension associated angiotensin
II (type 1) receptor C1166 allele. The same report
also revealed an increase in risk of nephropathy in diabetic patients
carrying a specific angiotensin II (type 1) receptor haplotype, i.e.
C1166/140-bp microsatellite allele (major allele).
Methods. In order to replicate these findings we
performed PCR-based genotyping for the A1166%rarr;C
DNA polymorphism and the CA repeat at the 3′ end of the
angiotensin II (type 1) receptor gene employing validated groups of type 1
diabetic patients with (cases, n=95) and without
(controls, n=97) nephropathy. HbA1 values above the
median (10.5) were used as an index of poor glycaemic control.
Results. The risk of nephropathy in carriers of the
C1166 allele with HbA1 < 10.5 was 2.1 (95% CI
0.8-5.2) compared to 1.1 (95% CI 0.4-2.6) for non-carriers of the
C1166 allele; however, these odds ratios were not
significantly different. No difference in the frequency of the high-risk
haplotype was found in cases compared to controls (12.4
vs 11.5; &khgr;2=0.01,
P=0.938 with 1 df). Conclusions.
The results of this study do not support previous findings that
the risk of diabetic nephropathy is associated with synergism between poor
glycaemic control and carriage of the C1166 allele
or inheritance of the C1166/major microsatellite
haplotype. Keywords: angiotensin II (type 1) receptor
gene; diabetic nephropathy; DNA polymorphism; glycaemic control;
insulin-dependent (type 1) diabetes mellitus; renin-angiotensin system
ORIGINAL ARTICLES
Risk of developing diabetic nephropathy is not associated with synergism between the angiotensin II (type 1) receptor C1166 allele and poor glycaemic control
Nephrology Research Group, The Queen's University of Belfast, Belfast, UK; Corresponding author address: Department of Medical Genetics, Floor A, Tower Block, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK; Present address: Section on Genetics and Epidemiology, Joslin Diabetes Centre, Boston, MA, USA
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