Renin-angiotensin system gene polymorphisms: its impact on IgAN and its progression to end-stage renal failure among Chinese in Singapore.
BACKGROUND
Gene polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (ATR) had been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasian and Japanese had reported contradicting results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese to assess their clinical impact.


METHODS
Genotyping was performed with DNA from peripheral leukocytes, PCR amplification of the polymorphic sequence, restriction enzymes digestion, separation and identification of DNA fragments. Clinical data at renal biopsy and final status on renal function were determined from patients' records.


RESULTS
Among controls, genotype distributions were in Hardy-Weinberg equilibrium. Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar whereas there was significant increase in the ACE DD genotype (p < 0.05). Comparing patients with end-stage renal failure (IgAN-ESRF) and without (IgAN-nonESRF), there was no difference in any of the three gene polymorphisms. But in contrast, there were significant differences in higher male prevalence (p < 0.05), increased serum creatinine at presentation (p < 0.05), more sclerosis (p < 0.01) and higher tubulointerstitial lesion score (p < 0.001) in the IgAN-ESRF group.


CONCLUSIONS
Among the ACE, AGT and ATR gene polymorphisms, only the DD genotype may predispose the individual to IgAN in our Chinese population. In contrast to clinical and histological risk factors, these genetic variations showed no impact on disease progression to ESRF. It is unlikely that genotyping more patients will prove these genes useful. Nevertheless, preclinically determined genetic markers are very useful as risk factors for disease occurrence and as prognostic indices for disease progression. Therefore, continuing efforts should be made to look at other genes to find those with significance.
Lau
Yeow-Kok
YK
Department of Renal Medicine, Singapore General Hospital, Singapore. grmlyk@sgh.com.sg
Woo
Keng-Thye
KT
Choong
Hui-Lin
HL
Zhao
Yi
Y
Tan
Hui-Boon
HB
Chong
Stephanie Mun-Chung Fook
SM
Tan
Eng-King
EK
Yap
Hui-Kim
HK
Wong
Kok-Seng
KS
D000328:Adult; D000808:Angiotensinogen / Q000235:genetics; D002681:China / Q000208:ethnology; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005922:Glomerulonephritis, IGA / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012846:Singapore
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A