Abstract
Purpose.:
To investigate the association of PLEKHA7 and COL11A1 with primary angle closure glaucoma, as well as acute and chronic subphenotype, in a Han Chinese population.
Methods.:
A total of 984 cases, including 606 primary angle closure glaucoma (PACG) and 378 primary angle closure (PAC), and 922 normal controls were recruited. Twelve single nucleotide polymorphisms (SNPs) (rs1676486, rs3753841, rs12138977, rs2126642, rs2622848, rs216489, rs1027617, rs366590, rs11024060, rs6486330, rs11024097, and rs11024102) in the PLEKHA7 gene and COL11A12 gene were genotyped. Distributions of allele frequencies were compared between cases and controls as well as in patient subgroups with or without acute attacks.
Results.:
Four of the 12 SNPs, including rs1676486 (P = 0.0060) and rs12138977 (P = 0.028) in COL11A1, as well as rs216489 (P = 0.0074) and rs11024102 (P = 0.038) in PLEKHA7, were found to have a statistically significant association with PAC/PACG. In the subgroup analysis, 6 out of 12 SNPs (rs1676486, rs3753841, rs12138977, rs216489, rs11024060, and rs11024102) showed statistically significant differences between acute PAC/PACG cases and controls. However, none of them showed statistically significant differences between chronic PAC/PACG cases and controls.
Conclusions.:
Our study suggests that rs1676486 and rs12138977 in COL11A1 as well as rs216489 and rs11024102 in PLEKHA7 are associated with an increased risk of PAC/PACG in the Han Chinese population, supporting prior reports of the association of COL11A1 and PLEKH7 with angle closure glaucoma. Both COL11A1 and PLEKHA7 were shown to confer significant risk for acute PAC/PACG. Further work is necessary to confirm the importance of COL11A1 and PLEKHA7 in the pathogenesis of glaucoma.
The study was approved by the ethical committee of Eye and Ear Nose Throat Hospital, Fudan University, and all procedures were conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from each individual.
The samples used in the study were collected in Eye and Ear Nose Throat Hospital. Each participant underwent a complete eye examination including best-corrected visual acuity, slit-lamp examination of the anterior chamber, measurement of intraocular pressure (IOP), and fundus photo assessment. Anterior chamber depth (ACD), axial length (AL), gonioscopy, and visual field were examined if PAC or PACG was suspected. Anterior chamber depth and AL were measured by A-scan ultrasound pachymetry. The biometric measurements of ACD and AL were excluded when the eye was pseudophakic or aphakic. The analysis of central corneal thickness (CCT), ACD, and AL was performed using the average data from both eyes. As there was high asymmetry between the two eyes for acute angle closure patients, analysis of IOP and cup-to-disc ratio was performed using the greater values.
The case group included PAC and PACG patients. Primary angle closure glaucoma was diagnosed using the definition from the International Society of Geographical and Epidemiological Ophthalmology (ISGEO).
12 Diagnosis was based on the presence of glaucomatous optic neuropathy with a cup-to-disc ratio ≥ 0.7, peripheral visual loss, an elevated IOP > 21 mm Hg, and the presence of at least two quadrants of iridotrabecular contact (ITC) in which the trabecular meshwork was not visible on gonioscopy. Primary angle closure eyes had features indicating that trabecular obstruction by the peripheral iris had occurred (peripheral anterior synechiae [PAS] or IOP > 21 mm Hg), but without glaucomatous optic neuropathy. Acute PAC/PACG was defined as an episode with (1) at least two of a list of symptoms (namely, ocular or periocular pain, nausea, vomiting, or an antecedent history of intermittent blurring of vision); (2) a presenting IOP > 28 mm Hg on Goldmann applanation tonometry; (3) at least three of a list of signs (namely, conjunctival injection, corneal epithelial edema, mid-dilated nonreactive pupil, and shallow anterior chamber [AC]).
13
A total of 984 PAC or PACG cases (PAC/PACG) and 922 normal controls were recruited. Among cases, there were 606 PACG and 378 PAC. The control group included ethnically matched individuals who were required to have none of the above-described characteristics, no family history of glaucoma, no previous surgeries for glaucoma, and no other ophthalmic diseases besides cataracts. Participants with secondary angle closure glaucoma due to uveitis, trauma, neovascularization, or any other optic nerve injury affecting either eye were excluded.
We thank all the PAC/PACG patients and normal controls for participating in this study. The samples used in this study were all from the Eye and Ear Nose Throat Hospital Biobank.
Disclosure: Y. Chen, None; X. Chen, None; L. Wang, None; G. Hughes, None; S. Qian, None; X. Sun, None
Supported by the National Natural Science Foundation of China (81200723) and Special Scientific Research Project of Health Professions of China (201302015). The authors alone are responsible for the content and writing of the paper.