Association Of LOC387715 And CFH Y402H Polymorphisms With Age-Related Macular Degeneration

【Purpose】To investigate association of LOC387715 and CFH Y402H polymorphisms with Age-Related Macular Degeneration.This study is to investigate the distribution of genotypes and alleles of LOC387715 and CFH gene Y402H polymorphisms in Age-related macular degeneration and healthy control group in North China and the correlation between these polymorphisms and age-related macular degeneration.【Method】Material:patients and heathy control subjects from Qilu hospital of Shandong University;Genomic deoxyribonucleic acid(DNA)was extracted from wet AMD patients and healthy control subjects,stored in -20℃.The genotypes of LOC387715 and CFH Y402H were detected by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP)methods in Age-related macular degeneration patients and controls.PCR amplification products were verificated by electrophoresis on agarose gel.Deviation of genotype distributions from Hardy-Weinberg equilibrium was assessed using a x² test in each group.The association between the genetic polymorphism and the disease was examined by x² test.Statistical analyses were performed with SPSS software calculating respectively each gene type frenquency in patients and control group.A P value＜0.05 was considered significant for statistical evaluations in comparision between groups using x² test.【Result】1,LOC387715:The frequency distribution of LOC387715 genotypes in Age-related macular degeneration patients was that 5.00%of patients as homozygous for the G allele,40.00%homozygous for the T allele,and 55.00%as heterozygous(GT),and the distributions of G alle and T alle of LOC387715 polymorphism were 32.50%and 67.50%respectively;and in healthy control group was that 39.51%of patients as homozygous for the G allele,12.10%homozygous for the T allele,and 48.39%as heterozygous(GT),and the distributions of G alle and T alle of LOC387715 polymorphism were 63.71%and 36.29%respectively.Hardy-Weinberg equilibrium:LOC387715 x²=2.57,P=0.11;CFH x²=0.27,P=0.61.There was a significant difference between Age-related macular degeneration patients and healthy control group in distribution of LOC387715 genotypes and of T alle of LOC387715 polymorphism(P＜0.05).OR_hom=26.13(5.38～126.80),OR_het=8.98(2.01～40.10).2,CFH Y402H:The frequency distribution of CFH Y402H genotypes in Age-related macular degeneration patients was that 75.00%of patients as homozygous for the T allele,2.50%homozygous for the C allele,and 22.50%as heterozygous(TC),and the distributions of T alle and C alle of CFH polymorphism were 86.25 and 13.75%respectively;and in healthy control group was that 92.10%of patients as homozygous for the T allele,0.88%homozygous for the C allele,and 7.02% as heterozygous(TC),and the distributions of T alle and C alle of CFH Y402H polymorphism were 95.61%and 4.93%respectively.Hardy- Weinberg equilibrium: LOC387715 x²=0.11,P=0.75;CFH x²=3.04,P=0.08.There was a significant difference between Age-related macular degeneration patients and healthy control group in distribution of CFH genotypes and of C alle of CFH polymorphism(P＜0.05). OR_hom=3.50(0.21～57.64),OR_het=3.94(1.40～11.09).3,Two-locus Odds Ratios for LOC387715 rs10490924 and CFH Y402H in wet AMD cases:We analyzed LOC387715 with the known CFH Y402H variant at 1q31. In particular,the association for LOC387715 in wet AMD remains significant conditional on the genotype at CFH Y402H for the individuals that also carry the CFH C risk allele.Two-locus analyses were performed for CFH Y402H variant at 1q31 and the LOC387715 polymorphism.OR_GT/TT=8.41(1.84～38.42);OR_GT/TC=10.75 (1.48～78.07);OR_GT/CC=21.50(0.96～483.70);OR_TT/TT=21.50(4.06～113.80).In all cases,the risk estimates indicate that genotypic combination with risk allele is at an increased risk over that of the common allele at both loci(GG/TT).Together LOC387715 and CFH Y402H risk variants increase the odds of having wet AMD.【Conclusions】1,LOC387715 gene and CFH gene exists a Single Nucleotide Polymorphisms (SNPs)in North China.Our results suggest that the LOC387715/CFH Y402H polymorphism may be associated with Age-related macular degeneration. LOC387715(G/T)and CFH Y402H(T/C)polymorphism are risk factors for Age-related macular degeneration.2,The research suggest that together LOC387715 and CFH Y402H risk variants increase the odds of having wet AMD.These findings expand the role of LOC387715 and CFHY402H in wet AMD.Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of wet AMD.3,This research suggest that both LOC387715 and CFH Y402H play a role in the pathogenesis of wet AMD,and provide a theory foundation of treatment and precaution of wet AMD.