The Role of the Gene–Gene and Gene–Environment Interactions of Polymorphic Loci of Matrix Metalloproteinases in Forming the Risk of Ischemic Stroke on the Background of Arterial Hypertension in Men

• Published in: Neuroscience and behavioral physiology Vol. 53; no. 4; pp. 496 - 502
• Main Authors: Kalinina, M. I., Ponomarenko, I. V., Efremova, O. A., Batlutskaya, I. V., Churnosov, M. I.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.05.2023; Springer Nature B.V
• Subjects: Alcohol abuse; Behavioral Sciences; Biomedical and Life Sciences; Biomedicine; Chromosome 11; Drug abuse; Environmental factors; Gene polymorphism; Genes; Haplotypes; Hypertension; Ischemia; Matrix metalloproteinase; Metalloproteinase; Neurobiology; Neurosciences; Single-nucleotide polymorphism; Stroke; matrix metalloproteinases; ischemic stroke; gene–environment interactions
• ISSN: 0097-0549; 1573-899X
• DOI: 10.1007/s11055-023-01447-z

Objectives. To analyze the role of genetic polymorphisms of matrix metalloproteinase ( MMP ) genes and their gene–gene and gene–environment interactions in the formation of ischemic stroke (IS) in men with arterial hypertension (AH). Materials and methods. The study included 523 men with hypertension: 201 with IS and 322 without stroke. The relationship between MMP loci and the formation of stroke in the presence of hypertension was determined by logistic regression analysis in dominant, recessive, and additive genetic models using PLINK v.2.050 software. Haplotype analysis was performed for five single nucleotide polymorphisms (SNP) co-located on chromosome 11 (314.3 kb), and associations of haplotypes with the development of stroke were identified using the EM algorithm. Gene–gene and gene–environment interactions between MMP and smoking and alcohol consumption in the development of stroke were assessed by the generalized multifactor dimensionality reduction (GMDR) method using GMDR v.0.9 software. Results. The rs3025058 polymorphic locus was found to be associated with IS in men in the dominant and additive genetic models (OR = 0.63–0.74, p perm = 0.03). Four MMP haplotypes had protective effects in relation to the development of stroke in the presence of hypertension (OR = 0.48–0.50, p perm = 0.02–0.03). Four models of gene–gene interactions of MMP polymorphic loci (OR = 2.19–2.55, p perm < 0.001) and three four-way models of gene–environment interactions of MMP with alcohol abuse (OR = 2.82–3.11, p perm < 0.001 ) were associated with high risks of developing IS in men with hypertension. rs3025058, rs1320632, rs11225395, and rs1799750 demonstrated the largest contributions to gene–gene and gene–environment interactions on formation of IS. Conclusions. The results obtained here indicate that the interactions of MMP genes with each other and with modifiable environmental factors play a significant role in the development of stroke on the background of AH in men.