Objective: To identify and evaluate MYOC variant alleles among patients with primary open-angle glaucoma (POAG) and age-matched control subjects in an Indian population.
Methods: Three hundred fifteen patients with POAG and 100 unrelated control subjects from the same ethnic background were enrolled in the study. The coding sequence of MYOC was amplified by polymerase chain reaction using genomic DNA, followed by sequencing of the polymerase chain reaction products. Four single nucleotide polymorphisms were genotyped in different Indian subpopulations comprising 1466 individuals using SEQUENOM's homogeneous MassEXTEND assay.
Results: One novel mutation (Gly399Asp), 6 reported mutations (Gln48His, Thr256Met, Thr353Ile, Gln368Stop, Pro370Leu, and Ala427Thr), and 6 single nucleotide polymorphisms were identified in MYOC. Ala427Thr was identified in a patient with POAG and Parkinson disease. Four single nucleotide polymorphisms genotyped in control subjects were highly heterozygous and displayed a similar pattern of linkage disequilibrium among all linguistic groups.
Conclusions: MYOC mutations account for 2.2% of POAG cases. The Gln368Stop mutation (common among persons of the white race) found in 2 families does not seem to be of white race origin. Identification of a MYOC mutation (Ala427Thr) in a patient with POAG and Parkinson disease is interesting with respect to reported interaction of myocilin with synucleins.
Clinical relevance: Studying the genetics of POAG is helpful for preclinical identification and for better disease management.