AUTHOR=Zhong Qiong-Qiong , Zhu Feng 

TITLE=Genetic loci, rs17817449 and rs6567160, known for obesity and the risk of stroke events among middle-aged and older Chinese people

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.1036750

DOI=10.3389/fneur.2022.1036750

ISSN=1664-2295

ABSTRACT=Background: The Fat Mass and Obesity-Associated (FTO) and the Melanocortin-4 Receptor (MC4R) genes are strongly associated with obesity which is an established risk factor for stroke. We aimed to assess the associations of rs17817449 at the FTO and rs6567160 at the MC4R with the risk of stroke events in middle-aged to older Chinese.
Materials and methods: Study data was obtained from the Guangzhou Biobank Cohort Study; a total of 148 participants with a self-reported stroke history, an equal volume of participants who were age- and sex-matched, were respectively selected as the cases and the controls in a case-control study; a total of 13,967 participants at the first follow-up and all participants with fatal stroke (up to April 2021) were included in a retrospective cohort study. Conditional logistic regression and the Cox proportional hazards regression analyses were used to assess the associations of the two genetic loci with the risk of stroke events.
Results: After adjusted for age, sex, education, job, smoke, alcohol drinking, the Body Mass Index, physical activity, hypertension, diabetes, and dyslipidaemia, rs17817449 and rs6567160 shared a minor allele G and C, respectively in the case-control analyses. The genotypes GG+GT of rs17817449 at the FTO were significantly associated with a decreased risk of fatal stroke occurrence, with fatal all strokes (adjusted hazard ratio (aHR)=0.71, 95% confidence intervals (CI) 0.52-0.97, P=0.04) and fatal ischeamic stroke (aHR=0.64, 95% CI 0.41-1.00, P=0.05), when the genotype TT was taken as a reference and a series of multiplicities were adjusted; the risk of fatal all strokes was lowered by dyslipidaemia (aHR=0.63, 95% CI 0.39-1.00, P=0.05) and non-diabetes (aHR=0.68, 95% CI 0.46-0.99, P=0.049) in the retrospective cohort analyses. Significances were observed in neither the associations of rs6567160 with the risk of stroke events nor an interaction between rs17817449 and rs6567160 in the two-stage analyses.
Conclusions: The G allele of rs17817449 at the FTO not rs6567160 at the MC4R was associated with a decreased risk of fatal stroke occurrence; its functional role in stroke should be explored in relatively healthy middle-aged to older Chinese.