| 저자 |
Hae-Yeon Park1*, Yeonjae Han2, Hye Mi Hwang2, Hyun-Mi Oh3, Tae-Woo Kim3, Geun-Young Park2, Joo Hyun Park1, Sun Im2† |
Background: Many genes may affect the outcome of stroke, and there have been studies suggesting that certain single nucleotide polymorphisms(SNPs), such as in brain-derived neurotrophic factor(BDNF), affect post-stroke motor recovery. Polymorphisms in certain genes may also affect dysphagia, which can be observed in about 40-60% of post-stroke patients. Common genetic variation on brain and behavior may be amplified with increased age. Certain SNPs may have more profound implications in aged individuals. The effect of age and genetic polymorphisms on stroke recovery have recently been highlighted. In previous studies, some SNPs related to catechol-O-methyl transferase(COMT), apolipoprotein E(APOE), and dopamine have been implicated in swallowing disturbances in the elderly. Based on the fact that age may affect SNPs, this study investigated whether SNPs have different effects on post-stroke dysphagia recovery in elderly vs. younger individuals.
Methods: This is post-hoc analysis from a prospective cohort study performed from a total of 218 subjects who met the inclusion criteria. Blood samples were obtained from the subjects and genotyping was done after informed consent for COMT(rs4680, rs165599), Dopamine receptor D1(DRD1, rs4532), Dopamine receptor D2 (DRD2, rs1800497), BDNF(rs1083521, rs6564), APOE(rs429358), and the Interleukin1 Receptor Antagonist Gene(IL1RN, rs4251961). Subjects were stratified into two groups, aged <65 (young) and ≥65 (elderly) years. Functional parameters and swallowing outcomes were measured at enrollment and 3 months post-onset.
Results: Total 206 patients were available for final analysis. Baseline characteristics between two age groups showed no significant difference except stroke type, aspiration pneumonia history, and thrombectomy history (Table 1). Swallowing and functional outcomes compared between the two age groups showed no significant group differences at baseline, and the proportion of patients with nil per mouth status at 12 weeks post-stroke onset (Table 2). However, by 3months post-stroke, elderly group showed poor outcome in aspiration severity and oral stages of swallowing (Table 2). Further analysis of association between genetic polymorphism and dysphagia stratified by age was performed. In the elderly group, minor allele of the DRD1(rs4532) polymorphism was associated with an increased risk of nil per mouth at 12-weeks post-stroke, both in the additive (OR=2.94; 95% CI 1.17-7.37) and dominant models (OR=2.93; 95% CI 1.04-8.23)(Table 3).
Conclusion: Our study suggests that there is a significant association between the DRD1 polymorphism and nil per mouth status risk in individuals aged≥65 years. This genetic polymorphism was not observed to influence the younger patient group. Factors that may influence swallowing recovery may differ between elderly and younger individuals, and SNPs should be taken into consideration in prognosticating post stroke dysphagia recovery, especially in the elderly. |
