title: Family-based analysis identified CD2 as a susceptibility gene for primary open angle glaucoma in Chinese Han population.
abstract: Primary open angle glaucoma (POAG) is characterized by optic disc cupping and irreversible loss of retinal ganglion cells. Few genes have been detected that influence POAG susceptibility and little is known about its genetic architecture. In this study, we employed exome sequencing on three members from a high frequency POAG family to identify the risk factors of POAG in Chinese population. Text-mining method was applied to identify genes associated with glaucoma in literature, and protein-protein interaction networks were constructed. Furthermore, reverse transcription PCR and Western blot were performed to confirm the differential gene expression. Six genes, baculoviral inhibitors of apoptosis protein repeat containing 6 (BIRC6), CD2, luteinizing hormone/choriogonadotropin receptor (LHCGR), polycystic kidney and hepatic disease gene 1 (PKHD1), phenylalanine hydroxylase (PAH) and fucosyltransferase 7 (FUT7), which might be associated with POAG, were identified. Both the mRNA expression levels and protein expression levels of HSP27 were increased in astrocytes from POAG patients compared with those from normal control, suggesting that mutation in CD2 might pose a risk for POAG in Chinese population. In conclusion, novel rare variants detected by exome sequencing may hold the key to unravelling the remaining contribution of genetics to complex diseases such as POAG.
authors.affiliation: Department of Ophthalmology, Daping Hospital & Research Institute of Surgery, Third Military Medical University of PLA, Chongqing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
authors.forename: Xiangge
authors.initials: X
authors.lastname: He
mesh_terms: D044466:Asian People; D018801:CD2 Antigens / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D055551:HSP27 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D009154:Mutation; D010375:Pedigree; D060066:Protein Interaction Maps
chemical_list: D018801:CD2 Antigens; D005136:Eye Proteins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones
keywords: Chinese population; exome sequencing; primary open angle glaucoma