Association of the transthyretin variant V122I with polyneuropathy among individuals of African ancestry.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
02 06 2021
Historique:
received: 08 02 2021
accepted: 21 05 2021
entrez: 3 6 2021
pubmed: 4 6 2021
medline: 6 11 2021
Statut: epublish

Résumé

Hereditary transthyretin-mediated (hATTR) amyloidosis is an underdiagnosed, progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. V122I, a common pathogenic TTR mutation, is found in 3-4% of individuals of African ancestry in the United States and has been associated with cardiomyopathy and heart failure. To better understand the phenotypic consequences of carrying V122I, we conducted a phenome-wide association study scanning 427 ICD diagnosis codes in UK Biobank participants of African ancestry (n = 6062). Significant associations were tested for replication in the Penn Medicine Biobank (n = 5737) and the Million Veteran Program (n = 82,382). V122I was significantly associated with polyneuropathy in the UK Biobank (odds ratio [OR] = 6.4, 95% confidence interval [CI] 2.6-15.6, p = 4.2 × 10

Identifiants

pubmed: 34079032
doi: 10.1038/s41598-021-91113-6
pii: 10.1038/s41598-021-91113-6
pmc: PMC8172853
doi:

Substances chimiques

Prealbumin 0
TTR protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

11645

Subventions

Organisme : CSRD VA
ID : IK2 CX001780
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

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Auteurs

Margaret M Parker (MM)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Scott M Damrauer (SM)

Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.

Catherine Tcheandjieu (C)

12 VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94304, USA.

David Erbe (D)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Emre Aldinc (E)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Philip N Hawkins (PN)

Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine UCL (Royal Free Campus), London, NW3 2PF, UK.

Julian D Gillmore (JD)

Centre for Amyloidosis & Acute Phase Proteins, Division of Medicine UCL (Royal Free Campus), London, NW3 2PF, UK.

Leland E Hull (LE)

Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Center for Healthcare Organization and Implementation Research, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, 01730, USA.

Julie A Lynch (JA)

School of Nursing & Health Sciences, University of Massachusetts, Boston, MA, 02125, USA.
VA Informatics and Computing Infrastructure (VINCI), VA Salt Lake City Health Care System, Salt Lake City, UT, 84148, USA.

Jacob Joseph (J)

Department of Medicine, Veterans Affairs Boston Healthcare System, Boston, MA, 02130, USA.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.

Simina Ticau (S)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Alexander O Flynn-Carroll (AO)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Aimee M Deaton (AM)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Lucas D Ward (LD)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Themistocles L Assimes (TL)

12 VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94304, USA.

Philip S Tsao (PS)

12 VA Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94304, USA.

Kyong-Mi Chang (KM)

The Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, 19104, USA.
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Daniel J Rader (DJ)

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Kevin Fitzgerald (K)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Akshay K Vaishnaw (AK)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Gregory Hinkle (G)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA.

Paul Nioi (P)

Alnylam Pharmaceuticals, 300 3rd St., Cambridge, MA, 02142, USA. pnioi@alnylam.com.

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Classifications MeSH