Association of the Thr377Met MYOC Mutation With IOP and Vertical Cup-to-Disc Ratios in a Small, Isolated Greek Population

Abstract

Purpose: : To determine if the Thr377Met MYOC mutation is associated with intraocular pressure (IOP), central corneal thickness (CCT) and vertical cup-to-disc ratio (VCDR) in Taxiarchis a small, isolated Greek village in which the incidence of the MYOC variant is extremely high.

Methods: : Six hundred villagers were enrolled in our study, 376 of whom were linked in a single 11 generation pedigree. Participants underwent a comprehensive ophthalmological exam. All three exons of myocilin were bidirectionally sequenced. Power calculations and measured genotype analysis was conducted using SOLAR version 4.2, in order to account for the relatedness between individuals.

Results: : The 600 participants ranged in age from 1 to 95 years with a mean age of 45. Seventy-eight villagers had the T377M MYOC variant. Fifty-eight individuals had POAG, 31 with the T377M mutation. Two of the POAG patients were homozygous for the T377M variant. Our power calculations indicate that we had 100% power to detect the observed effects of the T377M variant on our endophenotypes. Both peak IOP and vertical CDR were significantly associated with the MYOC T377M variant (p<9x10^-14 and p<9x10^-08, respectively), while CCT showed no significant association (p<0.7).

Conclusions: : In the cohort investigated T377M MYOC mutation is significantly associated with both high IOP and large VCDR ratio. No association was found with CCT.

Clinical Trial: : www.clinicaltrials.gov NCT00788762

Keywords: clinical (human) or epidemiologic studies: biostatistics/epidemiology methodology • genetics