Jacoby Ellie, Quan Dianna, Todd Emily, Shortt Jonathan, Smith Harry, Rafaels Nicholas, Crooks Kristy
Neurology Department, Neuromuscular Section, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Colorado Center for Personalized Medicine, Aurora, Colorado, USA.
Muscle Nerve. 2025 Feb;71(2):252-256. doi: 10.1002/mus.28301. Epub 2024 Dec 10.
INTRODUCTION/AIMS: Hereditary transthyretin amyloidosis (ATTRv) is a genetic condition caused by pathogenic variants in the transthyretin (TTR) gene resulting in multisystem amyloid deposition, especially in peripheral nerve and heart. Information on the prevalence of ATTRv in the United States is limited. The objective of this study was to understand the prevalence and genetic ancestry in the Val142Ile population in a large regional US population.
Colorado Center for Personalized Medicine (CCPM) biobank collects specimens from consenting adults seen throughout the University of Colorado Health System, a large tertiary healthcare system within the Rocky Mountain Region (RMR). Single nucleotide polymorphism (SNP) array genotyping and whole exome sequencing (WES) were performed for genetic research. Prevalence of TTR variants was studied.
A total of 73,346 participants had genetic testing; 151 (0.21%) individuals had a pathogenic or likely pathogenic TTR variant. The most common variant was Val142Ile, making up 82.61% of TTR variants found. Over four percent of people with African non-Hispanic ancestry had a Val142Ile variant.
The most common TTR variant in our study was Val142Ile, the most common variant in the United States (US). Similar to other US-based studies, affected individuals were predominantly of African, non-Hispanic ancestry. The availability of treatments for symptomatic ATTRv patients raises opportunities and challenges for biobanks as the identification of at-risk individuals places pressure on highly specialized centers and providers to see patients for screening and follow-up.
引言/目的：遗传性转甲状腺素蛋白淀粉样变性（ATTRv）是一种由转甲状腺素蛋白（TTR）基因的致病变异引起的遗传疾病，会导致多系统淀粉样沉积，尤其是在周围神经和心脏。关于美国ATTRv患病率的信息有限。本研究的目的是了解美国一个大型区域人群中Val142Ile人群的患病率和遗传血统。
科罗拉多个性化医学中心（CCPM）生物样本库收集了来自科罗拉多大学健康系统（落基山地区（RMR）的一个大型三级医疗系统）中同意参与的成年人的样本。进行单核苷酸多态性（SNP）阵列基因分型和全外显子组测序（WES）用于遗传研究。研究了TTR变异的患病率。
共有73346名参与者进行了基因检测；151人（0.21%）有致病性或可能致病性的TTR变异。最常见的变异是Val142Ile，占所发现的TTR变异的82.61%。超过4%的非洲非西班牙裔血统的人有Val142Ile变异。
我们研究中最常见的TTR变异是Val142Ile，这也是美国最常见的变异。与其他基于美国的研究类似，受影响个体主要是非洲非西班牙裔血统。针对有症状的ATTRv患者的治疗方法的出现，给生物样本库带来了机遇和挑战，因为识别高危个体给高度专业化的中心和提供者带来了压力，要求他们为患者进行筛查和随访。
