Mutations in the CYP1B1 Gene May Contribute to Juvenile-onset Open-angle Glaucoma

Overview

Journal Eye (Lond)

Specialty Ophthalmology

Date 2012 Aug 11

PMID 22878448

Citations 16

Authors

C-C Su

Y-F Liu

S-Y Li

J-J Yang

Y-C Yen

Affiliations

Soon will be listed here.

Abstract

Purpose: Glaucoma is one of the leading causes of blindness in the world. Juvenile-onset open-angle is a subtype of glaucoma. In this context, we investigate the possible mutations in the promoter and coding regions of the CYP1B1 gene among patients suffering juvenile-onset open-angle glaucoma (JOAG).

Methods: The CYP1B1 gene was analysed for mutations in 61 unrelated Taiwanese probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted from peripheral blood leukocytes and then subjected to PCR. The amplified products were screened for base mutations by autosequence. Next, data from the two groups were compared using the χ(2) test. Additionally, three-dimensional (3D) modelling of the human wild-type and p.R390H mutation was performed using SWISS-MODEL, an automated homology modelling program. Finally, the figure was prepared for the modelled structures by using the Accelrys ViewerLite 5.0 program.

Results: Analysis results indicated two CYP1B1 mutations and five polymorphisms. The prevalence of CYP1B1 gene mutations in this study was 4.92% (3/61). The mutations included a missense mutation (p.Arg390His; 2/3) and a mutation in the 5'-untranslated region (c.1-313A>C; 1/3). Moreover, computer-assisted modelling revealed that this p.R390H mutation affects the intra-molecular interaction in the hydrogen-bonding interaction with Glu387 and Asn428, thus altering significantly the efficiency of the haem-binding and proper folding of the molecule.

Conclusions: As a result, the p.Arg390His mutation might affect the protein structure and, ultimately, the normal function of CYP1B1. Therefore, we suggest that the c.1169G>A (p.Arg390His) mutation of CYP1B1 may be a risk factor for the development of JOAG.

Citing Articles

Identification and structural analysis of pathogenic variants in MYOC and CYP1B1 genes in Indian JOAG patients.

Yadav M, Kumar M, Dhull C, Sachdeva S, Bhardwaj A, Yadav A Jpn J Ophthalmol. 2025; .

PMID: 39998747 DOI: 10.1007/s10384-025-01173-8.

A rare optineurin mutation in an Indian family with coexistence of JOAG and PCG.

Yadav M, Yadav A, Bhardwaj A, Dhull C, Sachdeva S, Yadav R Indian J Ophthalmol. 2023; 71(8):3016-3023.

PMID: 37530275 PMC: 10538844. DOI: 10.4103/IJO.IJO_3383_22.

Molecular genetics of primary open-angle glaucoma.

Yadav M, Bhardwaj A, Yadav A, Dada R, Tanwar M Indian J Ophthalmol. 2023; 71(5):1739-1756.

PMID: 37203025 PMC: 10391438. DOI: 10.4103/IJO.IJO_2570_22.

Identification and Characterization of CYP6 Family Genes from the Oriental Fruit Moth () and Their Responses to Insecticides.

Han H, Yang Y, Hu J, Wang Y, Zhao Z, Ma R Insects. 2022; 13(3).

PMID: 35323597 PMC: 8953268. DOI: 10.3390/insects13030300.

Mutational analysis of (rs56010818) variant in primary open angle glaucoma (POAG) affected patients of Pakistan.

Narsani A, Waryah A, Rafiq M, Shaikh H, Naqvi S, Kumar R Saudi J Biol Sci. 2022; 29(1):96-101.

PMID: 35002398 PMC: 8716894. DOI: 10.1016/j.sjbs.2021.08.066.

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