CCR5-Δ32 polymorphism-a possible protective factor from gait impairment amongst post-stroke patients

Eur J Neurol. 2023 Mar;30(3):692-701. doi: 10.1111/ene.15637. Epub 2022 Dec 3.

Abstract

Background and purpose: Stroke and small vessel disease cause gait disturbances and falls. The naturally occurring loss-of-function mutation in the C-C chemokine receptor 5 gene (CCR5-Δ32) has recently been reported as a protective factor in post-stroke motor and cognitive recovery. We sought to examine whether it also influences gait and balance measures up to 2 years after stroke.

Method: Participants were 575 survivors of first-ever, mild-moderate ischaemic stroke or transient ischaemic attack from the TABASCO prospective study, who underwent a 3 T magnetic resonance imaging at baseline and were examined by a multi-professional team 6, 12 and 24 months after the event, using neurological, neuropsychological and mobility examinations. Gait rhythm and the timing of the gait cycle were measured by force-sensitive insoles. CCR5-Δ32 status and gait measures were available for 335 patients.

Results: CCR5-Δ32 carriers (16.4%) had higher gait speed and decreased (better) stride and swing time variability 6 and 12 months after the index event compared to non-carriers (p < 0.01 for all). The association remained significant after adjustment for age, gender, education, ethnicity and stroke severity.

Conclusions: Significant associations were found between gait measurements and CCR5-Δ32 loss-of-function mutation amongst stroke survivors. This is the first study showing that genetic predisposition may predict long-term gait function after ischaemic stroke.

Keywords: CCR5-Δ32 polymorphism; gait; insoles; stroke.

Publication types

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

MeSH terms

  • Brain Ischemia* / complications
  • Brain Ischemia* / genetics
  • Gait
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Ischemic Stroke*
  • Prospective Studies
  • Protective Factors
  • Receptors, CCR5 / genetics
  • Stroke* / complications
  • Stroke* / genetics

Substances

  • Receptors, CCR5
  • CCR5 protein, human