CFTR genotype analysis of Asians in international registries highlights disparities in the diagnosis and treatment of Asian patients with cystic fibrosis

Genet Med. 2022 Oct;24(10):2180-2186. doi: 10.1016/j.gim.2022.06.009. Epub 2022 Jul 20.

Abstract

Purpose: Cystic fibrosis (CF) is not well-characterized in Asians, potentially resulting in delayed diagnosis and poor prognosis. We characterized CF in Asian subgroups to address these disparities.

Methods: De-identified ethnicity and CFTR variant data were obtained from the United States, United Kingdom, and Canadian CF registries. We measured the prevalence of CF, CFTR variant allele frequencies, effectiveness of screening panels, and eligibility for modulator therapies.

Results: The prevalence of CF was 1 in 74,982 people (Canada) to 1 in 13,340 people (United Kingdom) for South Asians and 1 in 256,541 (Canada) to 1 in 52,563 (United Kingdom) for other Asians, suggesting 26,000 to 146,000 patients with CF in South Asia. p.(F508del) variant was markedly less frequent in Asians than in non-Hispanic Whites. Splicing and nonsense variants occurred at high allelic frequencies in Asians, resulting in 41% to 49% of South Asians and 21% to 39% of other Asians being ineligible for CFTR modulator therapies. Hologic/EU2v1 panels failed to identify 37% to 47% of South Asian and 23% to 46% of other Asian patients with CF.

Conclusions: Among Asians, CF appears to be more common in South Asians. A significant CF population may exist in South Asia. CFTR variants in South and other Asians markedly differ from non-Hispanic Whites causing inequities in newborn screening, diagnosis, and treatment. New strategies are necessary to mitigate these health care disparities.

Keywords: Modulator therapies; Newborn screening; Path to a cure; South Asians; The 10%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People* / genetics
  • Canada / epidemiology
  • Cystic Fibrosis Transmembrane Conductance Regulator* / genetics
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / ethnology
  • Cystic Fibrosis* / genetics
  • Genotype
  • Humans
  • Infant, Newborn
  • Mutation
  • Registries
  • United Kingdom / epidemiology
  • United States / epidemiology

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator