Accurate estimation of frequencies of 2 CYP1B1 PCG-cause mutation in regions of Guilan province
Ali Heshmati1 , Peyman Taghizadeh1 , Hassan Behboudi2 , Fatemeh Suri3 , Mahsa Alizadeh4 , Marjan Dadashzadeh5 , Hajar Khatami6 , Monireh Moradkhah Navi7 , Parisa Zamanparvar8 , Elahe Elahi1 *
- School of Biology, University College of Science, University of Tehran, Tehran, Iran
- Guilan University of Medical Science
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Astaneh Health Center, Astaneh, Guilan, Iran
- Rasht Health Center, Rasht, Guilan, Iran
- Anzali Health Center, Anzali, Guilan, Iran
- Talesh Medical Center, Talesh, Guilan, Iran
- Lahijan Medical Center, Lahijan, Guilan, Iran
Abstract: Primary congenital glaucoma (PCG) is the most severe form of glaucoma. Genetic factors significantly contribute to its etiology, and CYP1B1 is its most important causative gene. In an early study, it was shown that mutations in CYP1B1 were the cause of disease in approximately 70% of 100 Iranian patients studied. Among 19 different mutations identified, four were most frequent. Additionally, the western and north western regions of Iran had the highest prevalence of PCG, and the distribution of the mutations in various regions of Iran differed. Guilan was a province with high PCG prevalence. A subsequent study on 700 patients from Guilan, suggested that mutations p.G61E and p.R368H were frequent in, respectively, Talesh and eastern regions of Guilan. Here, we aimed to estimate the carrier frequencies of CYP1B1 mutations p.Gly61Glu and p.Arg368His in these regions with a maximum error of 2%.
Methods: Population based screenings were performed. DNA was extracted from septum samples of 1036 individuals from Talesh and 3029 individuals from the east of Guilan. P.Gly61Glu and p.Arg368His screenings were performed, respectively, by RFLP and ARMS-based PCR protocols. For confirmation, the DNA of individuals with mutations was sequenced using the Sanger protocol.
Results: Nine individuals from Talesh (0.86%; 95%CI: 0.45% - 1.64%) carried the p.Gly61Glu mutation, and 73 from the east of Guilan (2.41%; 95%CI: 1.91% - 3.04%) carried p.Arg368His. There was no significant difference in frequencies between urban and rural regions of the various cities, nor among four cities within the east of Guilan.
Conclusion: The frequencies of p.Gly61Glu carriers in Talesh and of p.Arg368His carriers in the east of Gilan were within the 95% confidence interval of the previous study based on screenings of fewer individuals. The reliability of the recent estimates is higher, as the confidence interval for p.Gly61Glu decreased from 6.5% to 1.19% and the interval for p.Arg368His decreased from 4% to 1.13%. Based on the new findings, the maximum expected frequency of p.Gly61Glu carriers in Talesh is 1.64%, and of p.Arg368His carriers in the east of Guilan is 3%. The appropriateness of performing pre-marital screenings in the respective cities can be evaluated.
