Ongoing controversies and recent insights of the ARMS2-HTRA1 locus in age-related macular degeneration

被引:15
作者
May, Adam [1 ,2 ,3 ]
Su, Fei [1 ,2 ,3 ,4 ]
Dinh, Brian [1 ,2 ,3 ,4 ]
Ehlen, Rachael [1 ,2 ,3 ,5 ]
Tran, Christina [1 ,2 ,3 ]
Adivikolanu, Harini [1 ,2 ,3 ]
Shaw, Peter X. [1 ,2 ,3 ]
机构
[1] Univ Calif San Diego, Viterbi Family Dept Ophthalmol, 9415 Campus Point Dr, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Shiley Eye Inst, 9415 Campus Point Dr, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Altman Clin & Translat Res Inst, 9452 Med Ctr Dr, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Div Cardiovasc Med, Dept Med, 9452 Med Ctr Dr, La Jolla, CA 92093 USA
[5] BlueNalu Inc, 6197 Cornerstone Court East, San Diego, CA 92121 USA
基金
美国国家卫生研究院;
关键词
Age-related macular degeneration; ARMS2-HTRA1 gene locus; Extracellular matrix; TGF-Beta signaling; Complement system; Linkage disequilibrium; SERINE-PROTEASE HTRA1; COMPLEMENT FACTOR-H; HIGH-TEMPERATURE REQUIREMENT; GENOME-WIDE ASSOCIATION; OXIDATIVE STRESS; EXTRACELLULAR-MATRIX; CHROMOSOME; 10Q26; RISK-FACTORS; SUSCEPTIBILITY GENES; RHESUS-MONKEYS;
D O I
10.1016/j.exer.2021.108605
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Age-related macular degeneration (AMD) is the most common cause of central vision loss among elderly populations in industrialized countries. Genome-wide association studies have consistently associated two genomic loci with progression to late-stage AMD: the complement factor H (CFH) locus on chromosome 1q31 and the age related maculopathy susceptibility 2-HtrA serine peptidase 1 (ARMS2-HTRA1) locus on chromosome 10q26. While the CFH risk variant has been shown to alter complement activity, the ARMS2-HTRA1 risk haplotype remains enigmatic due to high linkage disequilibrium and inconsistent functional findings spanning two genes that are plausibly causative for AMD risk. In this review, we detail the genetic and functional evidence used to support either ARMS2 or HTRA1 as the causal gene for AMD risk, emphasizing both the historical development and the current understanding of the ARMS2-HTRA1 locus in AMD pathogenesis. We conclude by summarizing the evidence in favor of HTRA1 and present our hypothesis whereby HTRA1-derived ECM fragments mediate AMD pathogenesis.
引用
收藏
页数:11
相关论文
共 127 条
[1]   Fragments of extracellular matrix as mediators of inflammation [J].
Adair-Kirk, Tracy L. ;
Senior, Robert M. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (6-7) :1101-1110
[2]   Elevated expression of serine protease HtrA1 in preeclampsia and its role in trophoblast cell migration and invasion [J].
Ajayi, Funminiyi ;
Kongoasa, Nicholas ;
Gaffey, Thomas ;
Asmann, Yan W. ;
Watson, William J. ;
Baldi, Alfonso ;
Lala, Peeyush ;
Shridhar, Viji ;
Brost, Brian ;
Chien, Jeremy .
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 2008, 199 (05) :557.e1-557.e10
[3]  
Akhtar-Schaefer I., 2019, SIGNALING MICROGLIA, P3
[4]   Bringing age-related macular degeneration into focus [J].
Allikmets, Rando ;
Dean, Michael .
NATURE GENETICS, 2008, 40 (07) :820-821
[5]   HtrA1 as a promising tissue marker in cancer: a meta-analysis [J].
Altobelli, Emma ;
Angeletti, Paolo Matteo ;
Morroni, Manrico ;
Profeta, Valerio Filippo .
BMC CANCER, 2018, 18
[6]   Identification of Novel Substrates for the Serine Protease HTRA1 in the Human RPE Secretome [J].
An, Eunkyung ;
Sen, Supti ;
Park, Sung Kyu ;
Gordish-Dressman, Heather ;
Hathout, Yetrib .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2010, 51 (07) :3379-3386
[7]  
Anand R, 2000, OPHTHALMOLOGY, V107, P2224
[8]   Characterization of β amyloid assemblies in drusen:: the deposits associated with aging and age-related macular degeneration [J].
Anderson, DH ;
Talaga, KC ;
Rivest, AJ ;
Barron, E ;
Hageman, GS ;
Johnson, LV .
EXPERIMENTAL EYE RESEARCH, 2004, 78 (02) :243-256
[9]   The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis re-visited [J].
Anderson, Don H. ;
Radeke, Monte J. ;
Gallo, Natasha B. ;
Chapin, Ethan A. ;
Johnson, Patrick T. ;
Curletti, Christy R. ;
Hancox, Lisa S. ;
Hu, Jane ;
Ebright, Jessica N. ;
Malek, Goldis ;
Hauser, Michael A. ;
Rickman, Catherine Bowes ;
Bok, Dean ;
Hageman, Gregory S. ;
Johnson, Lincoln V. .
PROGRESS IN RETINAL AND EYE RESEARCH, 2010, 29 (02) :95-112
[10]   Comprehensive Analysis of Complement Factor H and LOC387715/ARMS2/HTRA1 Variants With Respect to Phenotype in Advanced Age-Related Macular Degeneration [J].
Andreoli, Michael T. ;
Morrison, Margaux A. ;
Kim, Ben J. ;
Chen, Ling ;
Adams, Scott M. ;
Miller, Joan W. ;
Deangelis, Margaret M. ;
Kim, Ivana K. .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 2009, 148 (06) :869-874