Primary role of CYP1B1 in Indian juvenile-onset POAGpatients

[摘要] Purpose: CYP1B1, a member of the cytochrome P450 superfamily ofenzymes, has been implicated in primary congenital glaucoma (PCG).Recent studies suggest a role of CYP1B1 in primary open-angleglaucoma (POAG) as a modifier locus. The purpose of the study was tofurther investigate the potential role of CYP1B1 in POAG patients.Methods: Two hundred unrelated Indian POAG patients and 100unrelated ethnically matched controls were enrolled in this study. Thecoding sequence of CYP1B1 was amplified by polymerase chain reaction(PCR) from genomic DNA, followed by direct DNA sequencing to identifythe allelic variants.Results: Six mutations were identified in nine patients and none ofthe controls examined. One novel mutation (R523T) was detected in thehomozygous condition while three reported (W57C, E229K, and R368H) andtwo novel mutations (S515L and D530G) were found in the heterozygousstate. The homozygous mutation of a conserved residue, detected in afamilial juvenile onset POAG (JOAG) patient (lacking MYOC orOPTN mutations), cosegregated with the disease locus in an autosomalrecessive mode of transmission. All the novel mutations (R523T, S515Land D530G) were detected in a region of CYP1B1 that did not harborany of the 34 point mutations implicated in PCG. In addition, sixpreviously reported (p.R48G, p.A119S, p.V432L, p.D449D, p.N453S, and372-12C>T in intron 1) and four novel (p.V395V, p.P400P, p.V518A, andc.2016C>G in the 3'-UTR) single nucleotide polymorphism (SNPs) werealso observed in POAG patients and controls.Conclusions: Our observation suggests that on rare occasionsCYP1B1 may be primarily responsible for JOAG by possible monogenicassociation, and this observation emphasizes the importance of screeningfor mutation in this gene of JOAG patients that are determined not toharbor mutations in previously characterized candidate genes and locifor POAG.

[学科分类] 生物化学/生物物理