Abstract
BackgroundObstructive sleep apnea syndrome (OSAS) is strongly associated with the increasing prevalence of cerebrovascular events and metabolic syndrome. A growing number of studies have shown OSAS is an independent factor for insulin resistance, glucose intolerance and type2 diabetes. However, relationship of OSAS with dysglycemia is complex and still remains poorly understood. Glucose transporter 4 (GLUT4) gene is Human and rodents’ main glucose transporter sensitive to insulin, and therefore confirmation of candidate gene polymorphisms and association with OSAS is needed. Aim of our study was to assess whether GLUT4 gene polymorphisms are associated with OSAS.MethodsPatients hospitalized at People’s Hospital of Xinjiang were selected from January to December 2010. A total of 568 Han subjects who possibly exist OSAS base on a history and physical examination were completed the polysomnography, 412of whom (72.5%) were diagnosed with OSAS, and 156 individuals were confirmed without OSAS (27.5%). 96 severe OSAS patients chosen from OSAS were used for DNA sequencing in functional domain. Blood samples were collected from all subjects and genotyping was performed on DNA extracted from blood cells.ResultsWe performed GLUT4 genome sequencing, found 4 mutated sites. And finally selected three mutated sites such as rs5415, rs4517 and rs5435, according to principle of linkage disequilibrium (r 2 > 0.8) and minimum gene allele frequency > 5%. All SNPs satisfied HEW (P > 0.05). Our study demonstrated a significant association of GLUT4 SNPrs5417 allele with OSAS, compared with controls (P < 0.05). Haplotype H1 (TCC) and H3 (CCC) defined as SNPrs5415, rs4517 and rs5435 are marginally associated with OSAS (P < 0.05). Frequencies of C haplotype of rs5417 in OSAS were higher than in controls. After adjustment for confounding factors, (AC + AA) genotype significantly reduces prevalence of OSAS, compared with CC genotype. Level of awake blood oxygen and lowest blood oxygen of (AA + AC) genotype was significantly superior to those of CC genotype.ConclusionsOur study demonstrates GLUT4 gene SNPrs5417 is associated with OSAS in hypertensive population. Carriers of AA + AC have less prevalence of obstructive sleep apnea syndrome than that of CC carriers.
Highlights
Obstructive sleep apnea syndrome (OSAS) is strongly associated with the increasing prevalence of cerebrovascular events and metabolic syndrome
This study hypothesized indirectly, from molecular genetic mechanisms that OSAS causes dysglycemia phenotype, that OSAS might be associated with Glucose transporter 4 (GLUT4) gene polymorphism through GLUT4 gene mutation locus from sequencing screening
GLUT4 genetic sequence and based typing Our study found four locus in GLUT4 gene of 96 subjects with severe OSAS, according to linkage disequilibrium (LD) (r2 > 0.8) and minimum gene allele frequency > 5%
Summary
Obstructive sleep apnea syndrome (OSAS) is strongly associated with the increasing prevalence of cerebrovascular events and metabolic syndrome. All components of Metabolic syndrome, including hypertension [4,5], insulin resistance(IR) [6,7], and low HDL-C, together with high levels of TG [8,9] are frequent in patients with OSAS. In this context, OSAS was considered a “manifestation of MetS” [10]. Associated with insulin resistance and type 2 diabetes mellitus(DM), decrease in GLUT4 expression in cells and inhibition of its transposition are important factors causing dysglycemia [17,18]. We aim to provide new ideas for control of risk factors for cardiovascular diseases from molecular genetics aspects
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