Association of the ACE-II genotype with the risk of nephrotic syndrome in Pakistani children.
Nephrotic syndrome is a common pediatric glomerular disease associated with heavy proteinuria. Since, the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is a putative genetic risk factor for NS, in this study, ACE (I/D) polymorphism was analyzed in 268 NS and 223 control samples by a PCR-based method. The genotypic and allelic frequencies were determined and the association between ACE I/D polymorphism and NS was evaluated. The frequency distribution of the II, ID and DD genotypes was 82 (30.6%), 128 (47.8%) and 58 (21.6%) in the NS patients and 9 (4.0%), 171 (76.7%) and 43 (19.3%) in the control samples respectively. In the Pakistani pediatric NS population, the II genotypic and allelic frequencies were found to be significantly associated with the disease (OR=6.755; C.I=3-14.9). No significant association was found between this polymorphism and the response to standard steroid therapy. Thus, in contrast to reports from other parts of the world, the II genotype was found to be significantly associated with NS in the Indian and Malay populations and in the Pakistani population described here. To our knowledge, this is the first report from Pakistan describing the association of the ACE I/D polymorphism with pediatric NS. On the basis of these results, it is suggested that analysis of the ACE (I/D) polymorphism should be performed for the early diagnosis in the high risk NS patients in South Asia.
Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, Pakistan.
Saba
S
Shahid
Aiysha
A
Abid
Syed Qasim
SQ
Mehdi
Qasim Syed
QS
Mehdi
Sadaf
S
Firasat
Ali
A
Lanewala
Syed Ali Anwar
SA
Naqvi
Ali Anwar Syed
AA
Naqvi
Syed Adib-ul-Hasan
SA
Rizvi
Adib-ul-Hasan Syed
AU
Rizvi
Shagufta
S
Khaliq
D000293:Adolescent; D000085962:Angiotensin-Converting Enzyme 2; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010154:Pakistan; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013256:Steroids / Q000627:therapeutic use
D013256:Steroids; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2