Mutations and Polymorphisms in the Genes for Myocilin and Optineurin as the Risk Factors of Primary Open-Angle Glaucoma

• Published in: Russian journal of genetics 2005-11, Vol.41 (11), p.1295-1301
• Main Authors: Rakhmanov, V. V., Nikitina, N. Ya, Zakharova, F. M., Astakhov, Yu. S., Kvasova, M. D., Vasilyev, V. B., Golubkov, V. I., Mandelshtam, M. Yu
• Format: Article
• Language: English
• ISSN: 1022-7954; 1608-3369
• DOI: 10.1007/s11177-005-0232-4

A collection of DNA samples obtained from primary open-angle glaucoma (POAG) patients from St. Petersburg was analyzed for single-strand conformation polymorphism (SSCP) to reveal sequence variants in exon 3 of the myocilin gene (MYOC/TIGR) and in exons 4 and 5 of the optineurin gene (OPTN), where most of the mutations revealed worldwide are located. The Q368X mutation (c. 1102 C arrow right T) in exon 3 of MYOC/TIGR was detected in 1.2% (2/170) of the POAG patients from St. Petersburg, i.e., with the frequency close to that observed in other world populations. Three known polymorphisms in exon 3 of MYOC/TIGR were detected in glaucoma patients, namely Y347Y (c. 1041 T arrow right C) (12.4%), T325T (c. 975 G arrow right A) (0.6%), and K398R (c. 1193 A arrow right G) (0.6%). No statistically significant differences in frequencies of these polymorphisms were revealed between the POAG patient and control groups. The L41L polymorphism (c. 433 G arrow right A) in exon 4 of OPTN was detected in 2.9% of probands and in 1% of controls. The frequency of heterozygotes for the M98K polymorphism (c. 603 T arrow right A) in the OPTN exon 5 was statistically significantly higher (P = 0.036; Fisher's exact test) among the POAG patients (6.5%) than among the controls (1%). In the sample examined the E50K (c. 458G arrow right A) mutation, typical of the patients with pseudonormal intraocular pressure glaucoma (commonly known as low-tension glaucoma, LTG) was not found.