title: Variants at chromosome 10q26 locus and the expression of HTRA1 in the retina.
abstract: Variations in a locus at chromosome 10q26 are strongly associated with the risk of age-related macular degeneration (AMD). The most significantly associated haplotype includes a nonsynonymous SNP rs10490924 in the exon 1 of ARMS2 and rs11200638 in the promoter region of HTRA1. It is under debate which gene(s), ARMS2, HTRA1 or some other genes are functionally responsible for the genetic association. To verify whether the associated variants correlate with a higher HTRA1 expression level as previously reported, HTRA1 mRNA and protein were measured in a larger human retina-RPE-choroid samples (n = 82). Results show there is no significant change of HTRA1 mRNA level among genotypes at rs11200638, rs10490924 or an indel variant of ARMS2. Furthermore, two AMD-associated synonymous SNPs rs1049331 and rs2293870 in HTRA1 exon 1 do not change its protein level either. These results suggest that the AMD-associated variants in the chromosome 10q26 locus do not significantly affect the expression of HTRA1.
authors: John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. gwang@med.miami.edu.
authors: Gaofeng
authors: G
authors: Wang
authors: Sander R
authors: SR
authors: Dubovy
authors: Jaclyn L
authors: JL
authors: Kovach
authors: Stephen G
authors: SG
authors: Schwartz
authors: Anita
authors: A
authors: Agarwal
authors: William K
authors: WK
authors: Scott
authors: Jonathan L
authors: JL
authors: Haines
authors: Margaret A
authors: MA
authors: Pericak-Vance
mesh_terms: D000368:Aged; D002829:Choroid / Q000378:metabolism; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005786:Gene Expression Regulation / Q000502:physiology*; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism
chemical_list: C514392:ARMS2 protein, human; D017931:DNA Primers; D011506:Proteins; D012333:RNA, Messenger; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases
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