Polymorphism of renin-angiotensin system genes in IgA nephropathy.
OBJECTIVE
Individuals are prone to disease because of certain disease-susceptible genes. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, and the angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with IgA nephropathy (IgAN) and its progression. Several studies on Caucasians and Japanese patients have reported contradictory results. We determined these polymorphisms in 118 Chinese patients with IgAN and 94 healthy Chinese subjects to assess their clinical impact.


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


RESULTS
Comparing all IgAN patients with controls, AGT and ATR genotype distributions were similar, whereas there was a significant increase in the ACE DD genotype (P < 0.05). When comparing patients with end-stage renal failure (IgAN-ESRF) and those without (IgAN-nonESRF), there was no difference among the three gene polymorphisms. 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 the Chinese population. None are significant for prognosticating ESRF.
Woo
Keng-Thye
KT
Department of Renal Medicine, Singapore General Hospital, Singapore. grmwkt@sgh.com.sg
Lau
Yeow-Kok
YK
Choong
Lina Hl
LH
Zhao
Yi
Y
Tan
Hwee-Boon
HB
Fook-Chong
Stephanie
S
Tan
Eng-King
EK
Yap
Hui-Kim
HK
Wong
Kok-Seng
KS
D000328:Adult; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012084:Renin-Angiotensin System / Q000235:genetics*