The Association of Membrane Frizzled-Related Protein (Mfrp) Gene with Acute Angle-Closure Glaucoma - a Pilot Study

Purpose: The membrane frizzled-related protein (MFRP) has been proposed as a probable candidate gene for extreme hyperopia and nanophthalmos, which are factors for angle-closure glaucoma. The purpose of our study was to investigate whether there are significant associations between angle-closure glaucoma and sequence variants in the MFRP gene reported previously in Taiwanese subjects. Methods: Genomic DNA was collected from 63 subjects with angle-closure glaucoma and 66 age-matched and gendermatched controls without angle-closure glaucoma. Three sequence variants were detected by polymerase chain reaction (PCR) and direct sequencing in all of the cases and controls. Results: None of the three sequence variants showed a significant result in terms of association with disease. The pairwise linkage disequilibrium (LD) mapping confirmed that these alleles have a comparatively strong LD index greater than 0.7 for D' and greater than 0.4 for r2 at these polymorphisms. However, we found there were no statistical associations between any of the three sequence variants located on MFRP and angle-closure glaucoma. Conclusions: In our pilot study, variations that we tested in MFRP were not associated with the development of acute angle-closure glaucoma in Taiwanese subjects. Angle-closure glaucoma is an important cause of blindness in the Asian population particularly in those of Chinese and Taiwanese descent and may be acute, sub-acute, or chronic [1]. It has been established that primary angleclosure glaucoma (PACG) is associated with certain biometric ocular features such as shallow anterior chamber [2,3], increased thickness of the lens [4], and short axial length [5]. Such patients usually have a hyperopic refractive error [6]. The mechanisms involved in the pathophysiology and development of PACG are complicated and involve the anatomy of the anterior chamber angle as well as the spatial and anatomic relationships between the lens, iris, ciliary processes, and vitreous [7]. The pathophysiology of PACG usually involves an increase in lens thickness during the aging process, often in the setting of a relatively small eye and a shallow anterior chamber. By contrast, myopic eyes are typically longer and possess a thin sclera, particularly at the posterior pole. The human sclera of eyes with PACG and axial myopia undergo active remodeling and result in either excessive shortening or elongation of the axial length. Biochemical assays of highly myopic eyes show markedly reduced amounts of markers for collagen and