title: Molecular analysis of myocilin and optineurin genes in Korean primary glaucoma patients.
abstract: To investigate the underlying genetic influences of primary glaucoma in Korea, molecular analysis was performed in 112 sporadic cases, and results compared with healthy controls. The myocilin (MYOC) and optineurin (OPTN) genes were directly sequenced in 112 unrelated patients, including 17 with primary open‑angle glaucoma, 19 with juvenile open‑angle glaucoma, and 76 with normal tension glaucoma. Healthy unrelated Korean individuals (n=100) were used as the non‑selected population control. A total of three MYOC and four OPTN variants potentially associated with primary glaucoma were identified in 4 and 18 patients, respectively. A novel variant of MYOC, p.Leu255Pro, was predicted to be potentially pathogenic by in silico analysis. Another, p.Thr353Ile, has been previously reported. These two missense variants were detected in patients with a family history of glaucoma. Combined heterozygous variants p.[Thr123=;Ile288=] were identified in 2 of 112 (2%) patients but not in healthy controls. Among OPTN variants, a novel variant p.Arg271Cys was identified. Homozygous p.[Thr34=;Thr34=] (4/112, 4%), homozygous p.[Met98Lys;Met98Lys] (4/112, 4%), or combined heterozygous p.[Thr34=;Arg545Gln] (9/112, 8%) was significantly associated with the development of primary glaucoma [odds ratio (OR)=8.768, 95% confidence interval (CI)=1.972‑38.988; relative risk=1.818, 95% CI=1.473‑2.244; P=0.001]. The present study provides insight into the genetic or haplotype variants of MYOC and OPTN genes contributing to primary glaucoma. Haplotype variants identified in the present study may be regarded as potential contributing factors of primary glaucoma in Korea. Further studies, including those on additional genes, are required to elucidate the underlying pathogenic mechanism using a larger cohort to provide additional statistical power.
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Joonhong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Chan Kee
authors.initials: CK
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Chae
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Seungok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Yonggoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Woori
authors.initials: W
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine, Samkwang Medical Laboratories, Seoul 06742, Republic of Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Chi
authors.affiliation: Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Hae-Young Lopilly
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
authors.forename: Shin Hae
authors.initials: SH
authors.lastname: Park
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005901:Glaucoma / Q000175:diagnosis / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D056910:Republic of Korea; D035582:Transcription Factor TFIIIA / Q000235:genetics*; D000099179:Myocilin
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C409460:OPTN protein, human