Glaucoma-associated CYP1B1 mutations share similar haplotype backgrounds in POAG and PACG phenotypes.
OBJECTIVE
To understand the involvement of the CYP1B1 gene in cases of primary open-angle (POAG) and primary angle-closure (PACG) glaucomas and obtain the haplotype background of these mutations.


METHODS
The entire coding region of CYP1B1 was screened by resequencing in 224 unrelated cases of POAG (n = 134) and PACG (n = 90) and 200 ethnically matched normal control subjects from Indian populations. Six intragenic single nucleotide polymorphisms (SNPs) in CYP1B1 (-13T>C, R48G, A119S, V432L, D449D, and N453S) were used to generate haplotype data for the cases and controls and linkage disequilibrium (LD) and haplotype analysis were performed with Haploview software, which uses the EM (expectation-maximization) algorithm.


RESULTS
The frequency of CYP1B1 mutations was higher among POAG (18.6%; 95% CI, 12.9-26.1) than PACG (11.1%; 95% CI, 6.1-19.3) cases. There was a marked allelic heterogeneity, and the Arg368His was the most prevalent mutation across both the phenotypes. The spectrum of CYP1B1 mutations was largely similar across different POAG populations. Haplotypes generated with intragenic SNPs indicated the C-C-G-G-T-A to be a risk haplotype associated with CYP1B1 mutations in POAG (P = 0.006) and PACG (P = 0.043), similar to that observed in cases of primary congenital glaucoma worldwide.


CONCLUSIONS
The results demonstrate an involvement of CYP1B1 in a proportion of POAG and PACG cases that should be explored further. The similar haplotype background of these mutations is indicative of their common origin across multiple glaucoma phenotypes.
Chakrabarti
Subhabrata
S
Kallam Anji Reddy Molecular Genetics Laboratory, L. V. Prasad Eye Institute, Hyderabad, India. subho@lvpei.org
Devi
Koilkonda R
KR
Komatireddy
Sreelatha
S
Kaur
Kiranpreet
K
Parikh
Rajul S
RS
Mandal
Anil K
AK
Chandrasekhar
Garudadri
G
Thomas
Ravi
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002648:Child; D065633:Cytochrome P-450 CYP1B1; D004252:DNA Mutational Analysis; D015812:Glaucoma, Angle-Closure / Q000235:genetics*; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1