Association of variants in the ATXN2 (rs7137828), FOXC1 (rs2745572) and TXNRD2 (rs35934224) genes as risk factors for primary open-angle glaucoma development in a Brazilian cohort.

BACKGROUND: Primary open-angle glaucoma (POAG), the world's main cause of irreversible blindness, is an asymptomatic and neurodegenerative disease of multifactorial etiology with ethnic and geographic disparities. Multiethnic genome-wide association studies (GWAS) identified single nucleotide variants (SNVs) in ATXN2, FOXC1, and TXNRD2 loci as risk factors for POAG pathophysiology and/or endophenotypes. The aim of this case-control study was to investigate the association of the variants rs7137828 (ATXN2), rs2745572 (FOXC1), and rs35934224 (TXNRD2), as risk factors for POAG development, additionally to rs7137828 association with glaucoma clinical parameters in a Brazilian cohort from the Southeast and South regions. METHODS: This investigation comprised 506 cases and 501 controls. Variants rs2745572 and rs35934224 were genotyped through TaqMan® assays and validated by Sanger sequencing. Variant rs7137828 was genotyped exclusively by Sanger sequencing. RESULTS: The primary research outcome revealed that the variant rs7137828 (ATXN2) was associated with an increased risk for the development of POAG in the presence of the TT genotype compared to the CC genotype (p = 0.006; Odds Ratio [OR] = 1.717; Confidence Interval [CI] 95% = 1.169-2.535). There was no significant association of rs2745572 and rs35934224 genotypes with POAG. The CT genotype of the rs7137828 was associated with the vertical cup-to-disk ratio (VCDR) (p = .023) but not with the age at diagnosis or the mean deviation. CONCLUSION: Our data indicate the rs7137828 associated with increased risk for the development of POAG and VCDR in a Brazilian cohort. If validated in additional populations, these findings may enable the development of relevant strategies for early diagnosis of glaucoma in the future.

Correlation between retinal nerve fiber layer thickness and IOP variation in glaucoma suspects and patients with primary open-angle glaucoma.

PURPOSE: To analyze the relationship between retinal nerve fiber layer thickness (RNFLT) and intraocular pressure (IOP) variation in glaucoma suspects (GS) and patients with primary open-angle glaucoma (POAG). METHODS: Thirty-one GS and 34 POAG patients underwent ophthalmologic examination and 24-h IOP measurements. GS had IOPs ranging from 19 to 24 mmHg and/or suspicious appearance of the optic nerve. POAG patients had reproducible abnormal visual fields. We only included patients who presented with short-term IOP fluctuation >6 mm Hg (∆IOP). Only one eye per patient was included through a randomized process. Peripapillary RNFLT was assessed by spectral-domain optical coherence tomography. We correlated RNFLT with IOP parameters. RESULTS: Mean IOP was similar between GS and POAG groups (15.6 ± 3.47 vs 15.6 ± 2.83 mmHg, p = 0.90) as was IOP peak at 6 AM (21.7 ± 3.85 vs 21.3 ± 3.80 mmHg, p = 0.68). Statistically significant negative correlations were found in POAG group between IOP at 6 AM and RNFLT in global (rs = -0.543; p < 0.001), inferior (rs = -0.540; p < 0.001), superior (rs = -0.405; p = 0.009), and nasal quadrants (rs = -0.561; p < 0.001). Negative correlations were also found between ∆IOP and RNFLT in global (rs = -0.591; p < 0.001), and all other sectors (p < 0.05). In GS IOP at 6 AM correlated only with inferior quadrant (rs = -0.307; p = 0.047). CONCLUSION: IOP at 6 AM and ∆IOP had negative correlations with RNFLT quadrants in POAG. In GS this correlation occurred between IOP at 6 AM and inferior quadrant. These findings may indicate potential risk factors for glaucoma progression.

Investigation of CAV1/CAV2 rs4236601 and CDKN2B-AS1 rs2157719 in primary open-angle glaucoma patients from Brazil.

Large-scale genome-wide association studies have identified several susceptibility variants associated with the risk of primary open-angle glaucoma (POAG), among which rs4236601 (CAV1/CAV2) at chromosome 7q31 and rs2157719 at chromosome 9p21 (CDKN2B-AS1). The purpose of this study was to investigate whether these variants contribute to the incidence of POAG in a sample of the Brazilian Southeastern population and to determine the best-fitted genetic model for these single nucleotide polymorphisms (SNPs). A case-control study with 557 individuals, 310 with POAG, and 247 controls was conducted through PCR and direct sequencing. We observed a significant effect of the heterozygous genotype (G/A) of rs2157719 that occurred more frequently in the control group (p = 0.0004; OR: 0.517, CI 95%: 0.357-0.745). Allele frequencies also differed between cases and controls (p = 0.006; OR: 0.694, CI 95%: 0.522-0.922) with the best-fitted genetic model for rs2157719 being the codominant model. No differences were observed for genotype and allele distributions in relation to rs4236601 in the CAV1/CAV2 region. The association of rs2157719 (CDKN2B-AS1) with the POAG phenotype corroborates previously published results, reinforcing the importance of this variant in POAG etiology.