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Published on: April 4, 2018
Is paraoxonase 192 gene polymorphism a risk factor for membranoproliferative glomerulonephritis in children?
Ilmay Bilge1, Aydan Sirin, Bedia Agachan
1Istanbul University, Medical Faculty of Istanbul, Department of Pediatric Nephrology, Istanbul, Turkey. ilmaybilge@superonline.com.
Insights
The AA genotype of paraoxonase (PON1) 192 polymorphism is linked to an increased risk of developing membranoproliferative glomerulonephritis (MPGN) in Turkish children. This genotype also correlates with a poorer disease prognosis and lower serum PON1 activity.
Area of Science:
- Genetics
- Nephrology
- Biochemistry
Background:
- Paraoxonase (PON1) 192 polymorphism influences serum PON1 activity.
- Membranoproliferative glomerulonephritis (MPGN) is a serious kidney disease.
- The role of PON1 in MPGN risk and prognosis is not fully understood.
Purpose of the Study:
- To investigate the association between PON1 192 polymorphism and serum PON1 activity in Turkish children with MPGN.
- To determine the impact of PON1 genotype and activity on MPGN risk and prognosis.
Main Methods:
- Genotyping of PON1 192 polymorphism using PCR, RFLP, and agarose gel electrophoresis.
- Measurement of serum PON1 activity via spectrophotometric assay.
- Comparison of genotype frequencies and activity levels between MPGN patients and healthy controls.
Main Results:
- The frequency of the AA genotype was significantly higher in MPGN patients (61.1%) compared to controls (15.1%).
- Serum PON1 activity was generally lower in MPGN patients, though not statistically significant.
- PON1 activity increased with genotypes AA, AB, and BB in both patients and controls.
- A significant association was found between poor prognosis, AA genotype, and low PON1 activity.
Conclusions:
- Homozygosity for the PON1 A allele may increase the risk of developing MPGN in Turkish children.
- The AA genotype and low PON1 activity are associated with a poorer prognosis in pediatric MPGN.
- PON1 genetic variability significantly affects PON1 activity in Turkish MPGN patients.
Abstract:
We investigated the effects of paraoxonase (PON1) 192 polymorphism on serum PON1 activity and the impact of phenotypic expression on the risk and prognosis of Turkish children with membranoproliferative glomerulonephritis (MPGN). Eighteen children with biopsy-proven Type I MPGN (10 boys, 8 girls) and age-matched 53 healthy controls were included in the study. PCR (polymerase chain reaction), RFLP (restriction fragment length polymorphism) and agarose gel electrophoresis techniques were used to determine the PON1 192 genotype. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON1 192 genotype distribution (AA, AB, BB) in MPGN patients were 61.1%, 22.3%, 16.6% and 15.1%, 35.8%, 49.1% in controls, respectively. The frequency of AA genotypes was significantly higher in the MPGN group (0.611) compared with the healthy controls (0.151) (p < 0.001). Although the serum PON1 activity was lower in MPGN patients (103.3 +/- 55.2 U/l) than the healthy controls (130.9 +/- 71.2 U/mol), the difference was not statistically significant (p = 0.0563). In the genotypes of patients and controls classified according to PON1 A/B polymorphism; serum PON1 activities were significantly increased (p < 0.001, ANOVA) in the order of PON1 AA, AB and BB in both MPGN patients (82.4, 91.7 and 173.6 U/l) and healthy controls (85.9, 119.9 and 193.1 U/l), respectively. There was a significant relationship between the poor prognosis and having AA genotype and low PON1 activity. Of the 8 patients with poor prognosis, 7 had genotype AA and the remaining one was AB heterozygote. Our results suggest that homozygosity for the A allele might have an important role on the risk for developing MPGN and may also be associated with the poor prognosis of disease. In conclusion, we suggest that the PON1 activities are affected by PON1 genetic variability in Turkish patients with MPGN.
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