The Syntaxin-1A gene single nucleotide polymorphism rs4717806 associates with the risk of ischemic heart disease

Abstract

Ischemic heart disease (IHD) has a genetic predisposition and a number of cardiovascular risk factors are known to be affected by genetic factors. Development of metabolic syndrome and insulin resistance, strongly influenced by lifestyle and environmental factors, frequently occur in subjects with a genetic susceptibility. The definition of genetic factors influencing disease susceptibility would allow to identify individuals at higher risk and thus needing to be closely monitored. To this end, we focused on a complex of soluble-N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), playing an important role in metabolic syndrome and insulin resistance, involved in endothelial dysfunction and heart disease. We assessed if genetic variants of the SNARE genes are associated with IHD. SNAP25 rs363050 , Stx-1A rs4717806 , rs2293489 , and VAMP2 26bp ins/del genetic polymorphisms were analyzed in a cohort of 100 participants who underwent heart surgery; 56 of them were affected by IHD, while 44 were not. A statistical association of plasma glycemia and insulin resistance, calculated as Triglyceride glucose (TyG) index, was observed in IHD ( P < .001 and P = .03, respectively) after binomial logistic stepwise regression analysis, adjusted by age, gender, diabetes positivity, waist circumference, and cholesterol plasma level. Among genetic polymorphisms, rs4717806(A) and rs2293489(T) , as well as the rs4717806 – rs2293489 (A-T) haplotype were associated with higher risk for IHD ( Pc = .02; Pc = .02; P = .04, respectively). Finally, a statistical association of rs4717806(AA) genotype with higher TyG index in IHD patients ( P = .03) was highlighted by multiple regression analysis considering log-transformed biochemical parameters as dependent variable and presence of coronary artery disease, age, gender, waist circumference, presence of diabetes as predictors. These results point to a role of the Stx-1A rs4717806 SNP in IHD, possibly due to its influence on Stx-1A expression and, as a consequence, on insulin secretion and glucose metabolism.

SNAREs and developmental disorders

“…A SNP of STX1A was reported to correlate with age of onset and insulin requirement in type 2 diabetic patients (Tsunoda et al, 2001), while another variant in the STX1A promoter is associated with impaired glucose metabolism in an obese population (Romeo et al, 2008). A more recent report found a STX1A SNP rs4717806 to be associated with ischemic heart disease, possible due to its influence on STX1A expression and consequent dysfunctions insulin secretion and glucose metabolism (Guerini et al, 2019). A SNAP25 SNP, rs362551, was also found to be associated with the severity of metabolic syndrome in subjects with type 2 diabetes (Y. L. Chen et al, 2015).…”

Assessment of Stx-1A gene polymorphism (rs1569061) in relation to the development of multiple sclerosis in Egyptian patients

“…11 To allow exocytosis the amino terminal of SNAP25 binds to Stx-1A and the carboxy-terminal binds to VAMP2, forming the four-helical bundle that brings secretory granules in close contact with the plasma membrane, thus enabling fusion to occur. 12 The SNARE complex mediate exocytosis by forming a bundle that brings the two membranes together and forces their fusion. 13 Stx-1A protein, in particular, is widely expressed in the brain, in the endocrine system and in the heart.…”