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T. Yasuma, M. Nakamura, M. Kikuchi, K. Ishikawa, H. Nishihara, T. Yamakoshi, H. Terasaki; Association Between Systemic C-Reactive Protein Levels and Single Nucleotide Polymorphisms in HTRA1 and LOC387715. Invest. Ophthalmol. Vis. Sci. 2008;49(13):238. doi: https://doi.org/.
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It has been reported that systemic C-reactive protein (CRP) levels are elevated among patients with advanced age-related macular degeneration (AMD) (JAMA 2004, Ophthalmology 2007). On the other hand single nucleotide polymorphisms (SNPs) in the HTRA1 promoter (rs11200638) and adjacent putative gene LOC387715 (rs10490924) are strongly associated with AMD (Science 2006). Our aim was to determine the relationship between the CRP levels and these SNPs.
One-hundred and seventy-eight patients with neovascular AMD and 56 subjects without AMD or any macular abnormality were studied. The serum CRP level was measured by a high-sensitivity assay using a latex aggregation immunoassay. Genomic DNA was extracted from peripheral blood, and the genotypes were determined for the SNPs in HTRA1 and LOC387715. The CRP levels in the individuals with risk alleles were compared with that without risk alleles using the Kruskal-Wallis test. Associations between CRP levels and the genotypes were compared using logistic regression analysis by computing the odds ratios (ORs) and 95% confidence intervals (CIs) after the study populations were divided into quartiles.
In the AMD group, the median CRP levels among cases having the risk alleles were 0.101 mg/l for both rs11200638 (GA and AA genotypes) and rs10490924 (GT and TT genotypes). The values were significantly higher than that without the risk alleles for rs11200638 (GG genotype: 0.065 mg/l) and rs10490924 (GG genotype: 0.065 mg/l), respectively (p<0.05). After adjusting for baseline characteristics, cases in the higher quartiles of CRP had significantly increased risks to have the risk alleles for both rs11200638 (OR, 4.85; 95% CIs, 1.22-19.2) and rs10490924 (OR, 6.30; 95% CIs, 1.61-24.6). In subjects without AMD, the median CRP levels were 0.066mg/l and 0.070mg/l in those having the risk alleles for rs11200638 and rs10490924, respectively, and 0.051mg/l and 0.049mg/l in those without the risk alleles, respectively. The frequency of the risk allele for rs10490924 was significantly increased for the highest quartile of CRP (OR, 9.92; 95% CIs, 1.20-81.8).
We found significant associations between elevated serum CRP levels and disease-associated SNPs in HTRA1 and LOC387715. These results suggest that the SNPs are associated with inflammatory processes that may be underlying pathogenesis of AMD.
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