WD Repeat Domain 36 Gene Sequence Variants In Chinese Patients With Primary Open Angle Glaucoma

Glaucoma is an optic neuropathy with characteristic appearances of the optic disc and specific pattern of visual field defects that is associated frequently but not invariably with raised intraocular pressure. It is the second leading cause of blindness in the word. It has been estimated that the disease affects 66.8 million people, and 6.7 million of these have bilaterally blindness. Primary open-angle glaucoma(POAG)is the commonest form of adult glaucoma. It is a multi-factorial disease. The genetics play an important but complex role in it. So far, only three genes MYOCILIN(MYOC), OPTINEURIN(OPTN)and WD Repeat Domain 36 Gene(WDR36) have been identified as POAG disease causing gene. According to the previous studies, MYOC and OPTN showed a considerable ethnic disparity between Chinese and other populations. The prevalence of these two genes mutations was much lower than that in Caucasian. WDR36 gene for GLC1G on the long arm of chromosome 5, region q22.1 was the third POAG gene. It is reported to account for part of the POAG patients in Caucasian. However, so far, there is no information about this gene in Chinese population.In this study, we aim to discover sequence alterations in the WDR36 gene associated with POAG in Chinese subjects. 234 unrelated Chinese patients with POAG and 95 unrelated individuals without glaucoma, aged 50 years or more, were included. We use polymerase chain reaction(PCR), followed by fluorescent labeling automated DNA sequencing to detect the polymorphisms in WDR36 gene.Totally, eleven variants were detected, eight of which were missense changes(L25P, L92V, R95G, G103D, I175M, L240V, V259M and I264V)and three were synonymous codon changes (T180T, V714V, V727V). No variants were detected in noncoding sequence. Besides, in our study subjects we did not find any reported disease-causing mutations(N355S, A449T, R529Q and D658). However, we identified seven novel sequence variants(L92V, R95G, G103D, I175M, T180T, L240V and V259M). Furthermore, the WDR36 mutation frequency of 2.56ï¼…found in our Chinese population is much lower than that in other population, such as 5.02ï¼…in Americans in the original study and 17ï¼…in another study. Taking all these together, we suggest that there is an ethnic disparity between the WDR36 variants and POAG among Chinese and Caucasian populations.In our study, we have found that the common variants I264V, V714V and V727V were not associated with POAG. However, we also found that rare sequence variants: L25P, L92V, T180T, L240V and V259M appeared only in POAG patients, including juvenile open angle glaucoma, normal tension glaucoma and high tension glaucoma. Other three rare variants: R95G, G103D and I175M were detected exclusively in control subjects. These rare variants might confer additional risk or protective effects on POAG. Therefore our findings showed agreement to the assumption that WDR36 gene is most likely acts as a glaucoma modifier gene.