Association of single nucleotide polymorphisms in the CYP1B1 gene with the risk of primary open-angle glaucoma: a meta-analysis

Abstract

ABSTRACT. Mutations in the CYP1B1 gene were detected in primary openangle glaucoma (POAG) patients. However, the association between these mutations and the incidence of POAG remains to be elucidated. Here, we have conducted a meta-analysis to analyze this correlation, using relevant studies obtained from an extensive search of various electronic databases, including EMBase, Web of Science, and PubMed. The extracted studies were selected for the meta-analysis based on the inclusion and exclusion criteria. The quality of each included study was assessed by the Newcastle- Ottawa scale (NOS), and the I 2 value was calculated to evaluate the heterogeneity between studies. The combined effect size was presented as the odds ratio (OR), and confidence intervals (CI) were used to assess the association between POAG and CYP1B1 mutations. Eight studies, each with a high NOS score, were included in the analysis. Compared to the mutant allele, the wild-type allele of the rs180040 polymorphism in POAG patients showed a 12% decrease in OR (OR = 0.88, 95%CI = 0.76-1.00); also, the wild-type allele of rs1056827 showed a 23% decrease in OR of the incidence of POAG (OR = 0.77, 95%CI = 0.60-0.99). However, the latter result was controversial. Polymorphisms at rs1056836, rs10012, and rs1056837 were not correlated with the incidence of POAG (using any evaluation model). In conclusion, three of the tested SNPs in the CYP1B1 gene were correlated with POAG; however, the SNPs rs180040 and rs1056827 showed an association with risk of POAG. These results must be further validated with larger-scale evaluations.

Analysis of <em>CYP1B1 </em>sequence alterations in patients with primary open-angle glaucoma of Saudi origin

“… 1 However, two meta-analysis studies have found no association between CYP1B1 variants and POAG. 9 , 10 In accordance with these studies, our study also reports a negative association between CYP1B1 and POAG.…”

“…Our finding supports the conclusion reached by the recently conducted meta-analysis studies. 9 , 10 However, as with other complex diseases, including POAG, large sample numbers are needed to ensure sufficient power to identify the underlying genetic causal effect which may be a limiting factor in this study; besides, the presence of rare variants cannot be ruled out in this study, and as such, these findings need further validation in a larger cohort.…”

The association of estrogen-signaling pathways and susceptibility to open-angle glaucoma

“…Thus, ER polymorphisms may affect the physiological functions of estrogen in regulating aromatase and its product which later contributes to the development of OAG. Another possibility is that cyp1b1 (cytochrome P450 1B1) is regulated by ER [41], and the downregulation of this gene is correlated with OAG and oxidative stress in TM [42,43], although conflicting results regarding the role of polymorphism in cyp1b1 and the risk of OAG between studies were documented [40,42,44,45]. However, the loss of function in cyp1b1 variants, particularly c.1064_ 1076del, p.(Arg355Hisfs*69), seems to be associated with an increased risk for OAG [45].…”

Genetic Associations of Primary Angle-Closure Disease

“…In sensitivity analysis, we first excluded reports with fewer than 7 stars in the Newcastle Ottawa Scale assessment (eTable 1 in Supplement 1) 13,27 or cohorts deviating from Hardy-Weinberg Equilibrium in controls, 20,21,[49][50][51] then sequentially omitted each study 1 at a time and recalculated the pooled effect sizes. No significant alterations were observed, suggesting that the results were robust (data not shown).…”