Abstract
To explore the relationship between plasma C-reactive protein (CRP) levels, the main ARMS2 gene single nucleotide polymorphism (SNP), and gender in patients with neovascular age-related macular degeneration (wet AMD). Our study included 131 patients with wetAMD [age-related eye disease study (AREDS) category 4] and 153 control participants (AREDS category 1) from two Spanish retinal units. CRP levels were determined on blood samples by high-sensitivity ELISA assay. According to their CRP level, subjects were categorized into three well-established CRP categories: low (<1.00 mg/L, L-CRP), moderate (1-2.99 mg/L, M-CRP), and high (>3.00 mg/L, H-CRP). Genomic DNA was extracted from oral swabs using QIAcube (Qiagen, Hilden, Germany) and the A69S; rs10490924 of ARMS2 gene was genotyped by allelic discrimination with validated TaqMan assays (Applied Biosystems, Foster City, CA, USA). Univariate and multivariate logistic regression adjusted for age was used to analyze the genomic frequencies and to calculate odds ratio (OR) using SNPStats software. Considering CRP risk categories, H-CRP group showed a significant [OR 4.0 (1.9-8.3)] association with wetAMD compared to L-CRP group. The risk genotypes of A69S (TT) SNPs showed an association with wetAMD risk [OR 14.0 (4.8-40.8)]. Interestingly, the gender stratification of the CRP categories showed a significant increase in CRP levels in wetAMD women compared with control women [OR 6.9 (2.2-22.3)] and with wetAMD men [OR 4.6 (1.3-16.9)]. In addition, the subgroup analysis of CRP within A69S genotype and gender showed a link in women between the A69S and CRP levels in the AMD group compared to controls [OR 4.2 (1.4-12.6)]. Our study shows, for the first time, that a different genetic association related with gender could contribute to AMD risk. As a consequence, the risk of female gender in the different CRP levels and A69S SNP frequencies could be taken into consideration to the established risk relationship of high levels of CRP and its association with risk A69S genotype.
Highlights
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among people more than 55 years of age in developed countries and can be divided into early and late stages
To elucidate potential relationships between these factors, we aimed to investigate the influence of systemic C-reactive protein (CRP), A69S genotype, and gender in a large cohort of wetAMD patients and age-matched controls that attended in the Retinal units of two tertiary referral centers
H-CRP levels were observed in 46.6% of wetAMD individuals compared to a 31.4% in controls, whereas L-CRP levels were observed in 9.9% of wetAMD group compared to 26.8% of controls
Summary
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among people more than 55 years of age in developed countries and can be divided into early and late stages. Adaptive parainflammation (defined as low-grade chronic inflammation) exists in the aging retina under physiologic conditions, but unbalanced and uncontrolled parainflammation leads to a detrimental chronic inflammatory response and contributes to the development of early and advanced AMD forms. This chronic process is mediated by many genetic and environmental factors [6]. Systemic CRP, along with genetic variants in the inflammatory pathway (CFH) and other pathway (ARMS2) have been associated with advanced AMD in age-related eye disease study (AREDS) sub-population [15]. The relationship between CFH and CRP has been thoroughly studied by several authors, there is a paucity of high quality data directed to study the association between ARMS2 and CRP levels
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