Evaluation of the Obesity Genes FTO and MC4R for Contribution to the Risk of Large Artery Atherosclerotic Stroke in a Chinese Population

Background: Obesity is a well-established risk factor for large artery atherosclerotic (LAA) stroke. The aim of the study was to explore whether obesity genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han population. Methods: 322 LAA stroke patients and 473 controls were recruited. Gene polymorphism of MC4R (rs17782313) and FTO (rs8050136 and rs9939609) were genotyped. Results: No differences were observed in genotype frequencies of variants of FTO (rs8050136 and rs9939609) or MC4R (rs17782313) between LAA stroke patients and control subjects. However, rs17782313 of the MC4R gene was associated with LAA stroke susceptibility in smokers (rs17782313: p = 0.020, OR (95% CI) = 1.55 (1.07-2.23)) in the stratified analysis. Furthermore, multifactor dimensionality reduction analysis revealed that the combination of MC4R variant (rs17782313), hypertension and smoking habit was significantly associated with increased risk of LAA stroke (p < 0.0001, OR (95% CI) = 6.57 (4.79-9.01)). Conclusion: Our study indicated that the synergistic effects of MC4R variants, hypertension, and smoking habit contribute significantly to the risk of LAA stroke in the Chinese Han population. The finding revealed that obesity gene MC4R contribute to the risk of LAA stroke via a synergistic mechanism, which will provide new insight into the genetic architecture of LAA stroke.