Increased Risk of Multiple Outpatient Surgeries in African-American Carriers of Transthyretin Val122Ile Mutation Is Modulated by Non-Coding Variants

Journal of Clinical Medicine
Renato PolimantiJoel Gelernter

Abstract

Background: African-Americans (AAs) have a 3.5% carrier prevalence of Transthyretin (TTR) Val122Ile mutation (rs76992529), which is the genetic cause of a hereditary form of amyloidosis. Methods: We investigated the medical history of Val122Ile carriers and assessed the role of a non-coding variation in 4361 unrelated AAs. Results: We observed that the Ile122 allele was associated with a 6.8-fold increase in the odds of having 10 or more outpatient surgeries (p = 7.81 × 10-5). Stratifying the analysis by sex, the Ile122 allele was associated with a 15.2-fold increase in the odds of having 10 or more outpatient surgeries in men (p = 6.49 × 10-7). A similar sex difference was observed with respect to the association of Val122Ile with musculoskeletal and connective-tissue disorders in an independent cohort of British subjects (n = 361,194, p = 2.47 × 10-13; nmale = 167,020, pmale = 4.02 × 10-24). In Val122Ile African-American carriers, we observed that haplotypes in the upstream region regulating TTR hepatic expression are associated with having 10 or more outpatient surgeries (p = 2.56 × 10-9). Conclusions: TTR Val122Ile showed a large effect with respect to an extreme phenotype identified in medical history that may be related t...Continue Reading

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Citations

Jun 21, 2019·International Journal of Molecular Sciences·Gil Yong ParkSeong Soo A An
May 13, 2020·Journal of the Peripheral Nervous System : JPNS·Luca GentileAnna Mazzeo
Jan 12, 2021·Circulation. Genomic and Precision Medicine·Gita A PathakRenato Polimanti
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Methods Mentioned

BETA
genotyping

Software Mentioned

Haploreg
Plink
RegulomeDB
Haploview
Michigan Imputation Server

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