Wang Dy

Interactive Effects of ATOH7 and RFTN1 in Association with Adult-Onset Primary Open-Angle Glaucoma

PURPOSE Genome-wide association studies have shown association of the atonal homolog 7 (ATOH7) and raftlin lipid raft linker 1 (RFTN1) genes with glaucoma-related optic disc parameters. ATOH7 and RFTN1 sequence variations were investigated in patients with primary open-angle glaucoma (POAG) and their relationships with vertical cup-to-disc ratio (VCDR) and central corneal thickness (CCT) were determined. METHODS In 289 unrelated controls and 142 patients with adult-onset POAG, including 117 with high-tension glaucoma (HTG) and 25 with normal-tension glaucoma (NTG), the single exon of ATOH7 was sequenced by direct sequencing. Additional single-nucleotide polymorphisms (SNP) at upstream ATOH7 (rs1900004 and rs3858145) and an RFTN1 SNP (rs690037) were genotyped. Quantitative trait and disease associations were analyzed by linear and logistic regression respectively, controlling for sex and age. RESULTS ATOH7 rs61854782 was associated with VCDR (P = 0.004) in controls and RFTN1 rs690037 was associated with CCT in combined POAG (HTG+NTG; P = 0.026). No coding mutation was detected in POAG, and no SNP was associated with POAG (P between 0.441 and 0.996). However, ATOH7 rs3858145 showed significant interaction with RFTN1 rs690037 in NTG and combined POAG (P = 0.026 and 0.013 respectively). ATOH7 rs3858145 GG combined with RFTN1 rs690037 TT conferred risk for glaucoma in HTG, NTG, and combined POAG (odds ratio = 2.11, 8.44, and 2.69, respectively). CONCLUSIONS Coding mutations of ATOH7 were unlikely to be involved in POAG. But combination of ATOH7 and RFTN1 SNPs increased risk to POAG, indicating their diversified effects in the complex genetics of glaucoma.

Association analysis of cigarette smoking with onset of primary open-angle glaucoma and glaucoma-related biometric parameters

BackgroundTo date, studies on the role played by cigarette smoking in primary open-angle glaucoma (POAG) remains controversial. The current study evaluated cigarette smoking as a risk factor of POAG and its relationships with vertical cup-to-disc ratio (VCDR), central corneal thickness (CCT) and intraocular pressure (IOP) in a Chinese cohort.MethodsIn a total of 248 unrelated individuals including 30 juvenile-onset POAG (JOAG), 92 adult-onset POAG (AOAG) and 126 sex-matched senile cataract controls, underwent comprehensive ophthalmic examination. Their smoking was obtained and documented by questionnaire. Association of cigarette smoking with POAG was performed using logistic regression controlled for age and sex. Effects of cigarette smoking on VCDR, IOP and CCT were analyzed with multiple linear regression.ResultsIn either JOAG or AOAG, no association of cigarette smoking was found with disease onset (P = 0.692 and 0.925 respectively). In controls and JOAG, no significant effects of smoking were found on VCDR, IOP or CCT (all P > 0.05). Smoking was found to be correlated with decreased CCT in AOAG and combined POAG (JOAG + AOAG) (P = 0.009 and 0.003), but no association with VCDR or IOP was observed (P > 0.05).ConclusionsAlthough cigarette smoking was not found to be risk factor for onset of POAG, it was correlated with CCT in AOAG, and thus might still play a role in the disease course, especially for AOAG.