Role of MYOC and OPTN sequence variations in Spanishpatients with Primary Open-Angle Glaucoma

[摘要] Purpose: To retrospectively investigate the contribution ofmyocilin (MYOC) and optineurin (OPTN) sequencevariations to adult-onset ocular hypertension (OHT) and primaryopen-angle glaucoma (POAG) in Spanish patients.Methods: The promoter region and the three exons of MYOC wereanalyzed by direct PCR DNA sequencing in 40 OHT and 110 POAG unrelatedpatients. We used 98 subjects in whom OHT or glaucoma had been ruled outas controls. We also screened the complete coding region of the OPTNgene (exons 4-16) in all subjects by single-stranded conformationalpolymorphisms (SSCPs).Results: We identified six common single nucleotide polymorphisms(SNPs) in the promoter region of MYOC (-1000C>G, -387C>T,-306G>A, -224T>C, -126T>C and -83G>A) and a polymorphic GTmicrosatellite (-339(GT)11-19). In addition, we detected four novel,rare DNA polymorphisms. None of these DNA sequence variations wereassociated with either OHT or POAG. We also found three (2.7%) POAGpatients with MYOC pathogenic mutations. Two of these pathogenicmutations (Gln368Stop and Ala445Val) were previously described whereasthe third (Tyr479His) was novel. Transient expression of the novelmutation in 293T cells supported its pathogenicity. Only two OPTNpolymorphisms, which are not associated with the disease, weredetected.Conclusions: Overall, our data show that in Spain a minority ofadult-onset high-pressure POAG patients carry heterozygousdisease-causing mutations in the MYOC gene and that OPTN is notinvolved in either OHT or POAG.

[学科分类] 生物化学/生物物理