Different gender risk distribution of CRP and A69S frequencies in wet-AMD Spanish patients

Abstract

Purpose : We aimed to explore the relationship between main Single Nucleotide Polymorphisms (SNP) of CFH and ARMS2 genes, plasma C-reactive protein (CRP) levels and gender in neovascular Spanish patients of age related macular degeneration (wet-AMD).

Methods : Our study included 131 patients with wet-AMD (AREDS category 4) and 153 age and gender-matched control participants (AREDS category 1) from 2 Spanish hospitals: Clinica Universidad de Navarra and Hospital Clinic of Barcelona. CRP levels were determined on fasting samples by a high sensitivity ELISA assay (ICN, Pharmaceuticals). Subjects were categorized depending on their CRP level according to the three well-established CRP categories: low: <1.00 mg/L (L-CRP), moderate: 1 to 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 two principal SNPs (Y402H; rs1061170 of CFH gene and A69S; rs10490924 of ARMS2 gene) were genotyped by allelic discrimination with validated TaqMan assays (Applied Biosystems, Foster City, USA). Univariate and multivariate logistic regression adjusted for age was used to analyze the genomic frequencies and to calculate odds ratio (OR) by SNPStats software.

Results : Considering CRP risk categories, H-CRP group showed a significant [OR, 4.0; (1.9– 8.3)] association with the wet-AMD patients compared to L-CRP group. The risk genotypes of Y402H (CC) and A69S (TT) SNPs showed a strong association with risk of wet AMD [OR: 2.4, (1.3-4.6) and OR: 14.0, (4.8-40.8), respectively]. Interestingly, the gender stratification of the CRP categories showed a significant increase in CRP levels in wet AMD females compared with control females [OR 6.9 (2.2-22.3)] and with wet-AMD males [OR: 4.6, (1.3-16.9)]. In addition, the subdivision of CRP within Y402H, A69S genotypes and gender showed a strong association in females between the A69S and CRP levels in the AMD group compared to controls [OR 4.2 (1.4-12.6)].

Conclusions : Our study showed for the first time that a different genetic association related to gender is shown to contribute to AMD risk. Therefore, the risk of female gender in the different CRP levels and A69S SNP frequencies must be added to the established risk relationship of high levels of CRP and its association with risk Y402H and A69S genotypes. Gender must be considered in future studies analysis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.