Additive effects of genetic variants associated with intraocular pressure in primary open-angle glaucoma

被引：18

作者：

Mabuchi, Fumihiko ^{[1
]}

Mabuchi, Nakako ^{[1
]}

Sakurada, Yoichi ^{[1
]}

Yoneyama, Seigo ^{[1
]}

Kashiwagi, Kenji ^{[1
]}

Iijima, Hiroyuki ^{[1
]}

Yamagata, Zentaro ^{[2
]}

Takamoto, Mitsuko ^{[3
]}

Aihara, Makoto ^{[4
]}

Iwata, Takeshi ^{[5
]}

Kawase, Kazuhide ^{[6
]}

Shiga, Yukihiro ^{[7
]}

Nishiguchi, Koji M. ^{[8
]}

Nakazawa, Toru ^{[7
,8
,9
]}

Ozaki, Mineo ^{[10
]}

Araie, Makoto ^{[11
]}

机构：

[1] Univ Yamanashi, Dept Ophthalmol, Fac Med, Yamanashi, Japan

[2] Univ Yamanashi, Dept Hlth Sci, Fac Med, Yamanashi, Japan

[3] Tokyo Metropolitan Police Hosp, Dept Ophthalmol, Tokyo, Japan

[4] Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan

[5] Natl Hosp Org Tokyo Med Ctr, Natl Inst Sensory Organs, Div Mol & Cellular Biol, Tokyo, Japan

[6] Gifu Univ Hosp, Gifu, Japan

[7] Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Sendai, Miyagi, Japan

[8] Tohoku Univ, Grad Sch Med, Dept Adv Ophthalm Med, Sendai, Miyagi, Japan

[9] Tohoku Univ, Grad Sch Med, Dept Retinal Dis Control, Sendai, Miyagi, Japan

[10] Ozaki Eye Hosp, Miyazaki, Japan

[11] Kanto Cent Hosp, Mutual Aid Assoc Publ Sch Teachers, Tokyo, Japan

来源：

PLOS ONE | 2017年 / 12卷 / 08期

基金：

日本学术振兴会;

关键词：

TO-DISC RATIO; GENOME-WIDE ASSOCIATION; COMMON VARIANTS; RISK-FACTORS; FAMILY-HISTORY; POPULATION; HERITABILITY; PREVALENCE; EYE; SUSCEPTIBILITY;

D O I：

10.1371/journal.pone.0183709

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

To investigate the association between the additive effects of genetic variants associated with intraocular pressure (IOP) and IOP, vertical cup-to-disc ratio (VCDR), and high tension glaucoma (HTG) or normal tension glaucoma (NTG) as phenotypic features of primary open-angle glaucoma (POAG), and to evaluate the clinical usefulness of the additive effects of IOP-related genetic variants for predicting IOP elevation, Japanese patients with HTG (n = 255) and NTG (n = 261) and 246 control subjects were genotyped for nine IOP-related genetic variants near CAV2, GAS7, GLCCI1/ICA1, ABCA1, ARHGEF12, FAM125B, FNDC3B, ABO, and PTPRJ/AGBL2. The total number of risk alleles of these genetic variants was calculated for each participant as a genetic risk score (GRS), and the association between the GRS and the maximum IOP, mean VCDR, and phenotype (HTG or NTG) of POAG was evaluated. As the GRS increased, the maximum IOP (P = 0.012) and VCDR (P = 0.010) significantly increased. The GRS (9.1 +/- 1.9) in patients with HTG was significantly higher (P = 0.011) than that (8.7 +/- 1.8) in control subjects. The patients with GRS >= 12 as a cut-off value had a 2.54 times higher (P = 0.0085) risk on HTG (maximum IOP >= 22mmHg) compared with all patients. The IOP-related GRS approach substantiated that the IOP and VCDR were increased by the additive effects of IOP-related genetic variants in POAG. The high IOP-related GRS in patients with HTG but not NTG shows that there are differences in the genetic background between HTG and NTG and supports the notion that the phenotype (HTG or NTG) in patients with POAG depends on the additive effects of IOP-related genetic variants. The above-mentioned cut-off value of IOP-related GRS may be clinically useful for predicting the risk of IOP elevation.

引用

页数：13

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