Abstract
BACKGROUND: Obstructive 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. METHODS: Patients 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. RESULTS: We 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 (r2 > 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. CONCLUSIONS: Our 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.