Abstract
Purpose: :
Recently 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. We investigated ATOH7 and RFTN1 sequence variations in patients with primary open angle glaucoma (POAG) and their relationships with vertical cup-to-disc ratio (VCDR) and central corneal thickness (CCT).
Methods: :
In 289 unrelated controls and 142 unrelated adult-onset POAG, the single exon of ATOH7 was sequenced by direct sequencing after PCR. Additional single nucleotide polymorphisms (SNP) at upstream ATOH7 (rs1900004 and rs3858145) and a RFTN1 SNP (rs690037) were genotyped by Taqman assays. Quantitative trait and disease associations were analyzed by linear and logistic regression respectively, controlling gender and age.
Results: :
ATOH7 rs61854782 was associated with VCDR (P = 0.004) in controls and RFTN1 rs690037 was associated with CCT in POAG (P = 0.026). No coding mutation in ATOH7 was detected in POAG. None of the SNP investigated was associated with POAG (P-values between 0.441 and 0.996). However, SNP rs3858145 in ATOH7 showed significant interaction with RFTN1 rs690037 inPOAG (P = 0.013). ATOH7 rs3858145 GG combined with RFTN1 rs690037 TTconferred risk to glaucoma in POAG (odds ratio = 2.69).
Conclusions: :
Coding mutations of ATOH7 are unlikely to be involved in adult-onset POAG. But combination of ATOH7 and RFTN1 SNPs increased risk to POAG, indicating their diversified effects in the complex genetics of glaucoma.
Keywords: gene modifiers • optic disc • intraocular pressure