Association of CFH, LOC387715, and HTRA1 polymorphisms with exudative age-related macular degeneration in a northern Chinese population

Yule Xu, Ning Guan, Jun Xu, Xiufen Yang, Kai Ma, Haiying Zhou, Feng Zhang, Torkel Snellingen, Yiqun Jiao, Xipu Liu, Ningli Wang, Ningpu Liu, Yule Xu, Ning Guan, Jun Xu, Xiufen Yang, Kai Ma, Haiying Zhou, Feng Zhang, Torkel Snellingen, Yiqun Jiao, Xipu Liu, Ningli Wang, Ningpu Liu

Abstract

Purpose: Variants in complement factor H (CFH), the hypothetical LOC387715, and the high-temperature requirement A-1 (HTRA1) genes have been reported to be associated with age-related macular degeneration (AMD). The purpose of this study was to investigate the association of reported common single-nucleotide polymorphisms (SNPs) in CFH, LOC387715, and HTRA1 with exudative AMD in a northern Chinese population.

Methods: A cohort of 121 unrelated patients with exudative AMD and 132 control subjects were enrolled in this study. Genomic DNA was extracted from blood leukocytes. Genotyping for SNPs rs1061170:T>C in CFH (Y402H), rs10490924:G>T in LOC387715 (A69S), and rs11200638:G>A in the promoter of HTRA1 was performed using a polymerase chain reaction (PCR) method followed by allele-specific restriction enzyme digestion and direct sequencing.

Results: The Y402H variant in CFH was not associated with exudative AMD in our study population. Frequencies of Y402H was 10.3% in AMD cases and 8.0% in controls (p=0.353). Significant associations were detected for exudative AMD with SNPs rs10490924:G>T in LOC387715 (A69S), and rs11200638:G>A in the promoter of HTRA1. The risk T-allele frequency of rs10490924 in LOC387715 was 64.9% in cases versus 43.2% in controls (p<0.001). The odds ratio for risk of AMD was 1.56 (95% CI; 0.80-3.03) for the GT genotype and 5.45 (95% CI; 2.59-11.49) for the TT genotype. The A allele frequency of rs11200638 in the HTRA1 promoter was 67.8% in cases versus 42.4% in controls (p<0.001). The odds ratio was 2.75 (95% CI; 1.34-5.64) for the GA genotype and 7.90 (95% CI; 3.61-17.26) for the AA genotype. An odds ratio of 7.94 (95% CI; 3.49-18.04) was obtained for carriers with both TT genotype in LOC387715 and AA genotype in the HTRA1 promoter.

Conclusions: Our data suggest that the LOC387715 and HTRA1 polymorphisms are associated with a higher risk of exudative AMD in northern Chinese. We found no association of CFH Y402H with exudative AMD. The low frequency of CFH Y402H variant was further confirmed in this study population.

Figures

Figure 1
Figure 1
Ethidium bromide-stained 2% agarose gels and direct sequencing, showing the PCR-restriction fragment length polymorphism and corresponding sequence chromatogram. A: Restriction analysis for complement factor H (CFH) Y402H polymorphism resulted in digestible fragment (T/T), undigestible fragment (C/C), and heterozygote (T/C). B: Direct sequencing of the PCR products confirmed the restriction patterns for CFH Y402H. C: Restriction analysis for LOC387715 rs10490924 resulted in digestible fragment (G/G), undigestible fragment (T/T), and heterozygote (T/G). D: Sequencing confirmed the restriction patterns for LOC387715 rs10490924. E: Restriction analysis for HTRA1 rs11200638 resulted in digestible fragment (G/G), undigestible fragment (A/A), and heterozygote (G/A). F: Sequencing confirmed the restriction patterns for HTRA1 rs11200638.

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