Table 1 Main characteristics of the studies included in the analysis

Colomb et al. [59]

Retrospective

Patients affected by primary open-angle glaucoma (POAG) diagnosed by the conjunction of a characteristic cupping of the optic disk, an open iridocorneal angle (grade III or IV gonioscopy), and an alteration of the visual field, tested by automated perimetry (with Humphrey’s perimeter or Octopus). Elevated intraocular pressure (IOP) > 21 mmHg by applanation tonometry on at least two examinations. N = 117

All baseline differences were not statistically signifcant, apart from IOP and visual field. Total controls N = 94; allele control N = 25

French

Not reported

Trabecular meshwork-inducible glucocorticoid response (TIGR)/MYOCILIN

(MYOC) MYOC.mt1

Topical beta-blockers that could be associated with miotics

Slower decrease of IOP in comparison with the non carriers of the allele and female patients did not show any reduction of IOP

Cui et al. [60]

Prospective study

POAG was defined by the criteria of the International Society of Geographic and Epidemiological Ophthalmology (ISGEO) [7]: an untreated Intraocular pressure (IOP) of 21 mmHg or more with a Goldman applanation tonometery, open anterior chamber angles on gonioscopy; glaucomatous optic disc changes (increased cup/disc ratio, thinning of the neuroretinal rim, notching) on ophthalmoscopy and visual field defects characteristic of glaucoma by standard automated perimetry with the Humphrey Visual Field Analyzer. N = 135 divided per each genotype

PTGFR rs3766355 A > C was associated to higher pre-treatment IOP (P < 0.05)

Not reported

HWE was tested by chi-square test and genotypes conformed to it

rs11723068 G > A and rs757253 T > C of the Actin filament-associated protein (AFAP) gene; rs9503012 C > T and rs17134549 T > A of the GDP-mannose 4,6 dehydratase (GMDS) gene; rs3753380 C > T and rs3766355 A > C of the prostaglandin F2 receptor negative regulator (PTGFR)

Latanoprost

TT genotype of GMDS rs9503012 C > T as well as AA genotype of PTGFR rs3766355 A > C was correlated with a statistically significant better response to the therapy with latanoprost. On the contrary, age, CC + CT genotypes of GMDS rs9503012 C > T and CC + AC genotypes of PTGFR rs3766355 A > C were associated with worse response to latanoprost

Gao et al. [61]

Prospective registered in the Chinese Clinical

Trial Registry (registration number: ChiCTR-OCC-

11,001,326)

POAG, N = 60 divided per each genotype

No significant baseline differences, as reported in supplementary materials S1 (P > 0.05)

Chinese

HWE was analyzed by using Pearson χ2 test of goodness-of-fit in the study sample proving respected

Prostaglandin-endoperoxide synthase 1 (PTGS1) (rs3842787 and rs10306114); PTGFR (rs3753380 and rs3766355); multidrug resistance protein 4 (MRP4) (rs11568658 and rs11568668)

Latanoprost

No difference in frequency and type of side effects after treatment with latanoprost, but 3435C > T (CC and TT mainly) genotype frequency distribution was significantly higher in the group experiencing effectiveness (P = 0.002 and P = 0.001, respectively)

Liu et al. [62]

Case–control study

The diagnosis of POAG was based on diagnostic criteria published by the Chinese Medical Association Glaucoma Branch in 2008. The criteria for diagnosis of POAG were as follows: (1) IOP ≥ 21 mmHg; (2) abnormal optic disc determined by optical coherence tomography; (3) glaucomatous visual field deletion (on the basis of mean deviation and corrected pattern standard deviation); (4) retinal nerve fiber layer defect; and (5) open anterior chamber angle N = 93

No baseline differences (P > 0.05). N = 125

Han subjects in this study were not blood relatives

All patients with different allelic and genotypic frequencies were in HWE

ATP-binding cassette sub-family B member 1 (ABCB1), also known as MRP4

Latanoprost

No difference in the frequency and type of side effects after treatment with latanoprost, but 3435C > T (CC and TT mainly) genotype frequency distribution significantly higher in the group showing efficacy of latanoprost (P = 0.002 and P = 0.001, respectively)

Liu et al. [63]

Prospective study

POAG defined as early stage, but without defining the criteria. N = 129

One hundred and twenty one age and gender matched healthy people in the same geographical area were randomly selected and identified as the control group. Baseline characteristics do not significantly differ (P > 0.05)

Not reported, but Yunnan Province was specified as geographical area

Genotype frequency distributions of ABCB1 gene polymor-phisms-129T > C, 1236C > T, 2677G > T/A and 3435C > T in the case group and the control group were in HWE

Cytochrome P450 2C19 (CYP2C19)

Timolol

In the two groups developing side effects or showing absence of side effects the frequencies of extensive metabolizer phenotype and poor metabolizer phenotype or poor metabolizer phenotype and intermediate metabolizer phenotype were significantly different (both P < 0.05), but not between intermediate metabolizer phenotype and extensive metabolizer phenotype (P > 0.05). Side effects are more frequent in the group of the poor metabolizers

Ussa et al. [64]

Multicenter case–control study of 5 participating centers

Diagnosis of POAG according to the American Academy of Ophthalmology preferred practice pattern guidelines, optic disc or retinal nerve fiber layer abnormalities, reproducible visual field abnormality and open anterior chamber angles. N = 124

A total of 117 DNA samples could be used for the study: 98 (83.8%) represented the group of responders, among whom 8 (7.7%) were hyperresponders, and 19 (16.2%) were nonresponders. No significant baseline differences apart from IOP

Caucasian, Spanish

HWE was assessed with the Pearson goodness-of-fit test or Fisher exact test when there was a low genotype count. HWE was verified for all the polymorphisms apart from rs7545762 (PTGFR) showing an inconsistent distribution in the nonresponder group

rs6686438 and rs1328441 (PTGFR), rs10489950 and rs3753380 (MMP-1), polymorphisms of MMP-2, -3, -9, and -17

Latanoprost

Polymorphisms of PTGFR, as well as of the gene coding for matrix metalloproteinases 1 (MMP-1), were found to influence the effectiveness of the treatment

Yang et al. [29]

Prospective study

POAG diagnosed as intraocular hypertension (IOP ≥ 21 mmHg), glaucomatous visual fi eld deletion (on the basis of mean deviation and corrected pattern standard deviation, or corrected loss variance of standard 30/II Humphrey perimetry), and abnormal optic disc as determined by the optical coherence tomography. N = 133, but N = 73 were included in genotyping

There were no significant baseline differences among subjects with Arg296Cys or Ser486Thr genotypes

(P > 0.05)

The genotype frequencies approached corresponding data of Asian people declared on the NCBI Web page (http://www.ncbi.nlm.nih.gov/) in HWE

Genotypes for Pro34Ser were not in HWE

Eight polymorphisms of CYP2D6

Timolol

Genotypes Arg296Cys and Ser486Thr did not significantly affect IOP. Arg296Cys CT and TT genotype were significantly more predisposed to develop bradycardia than CC (P = 0.009)

Yuan et al. [65]

Prospective study

POAG N = 123

Not reported

rs16947 (2850C > T, R296C) and rs1135840 (4180C > G, S486T) polymorphims of CYP2D6

Timolol

rs16947 (2850C > T, R296C) and rs1135840 (4180C > G, S486T) did not influence the IOP lowering effect induced by timolol (P = 0.339 and P = 0.903, respectively)