| Objective There is a relationship between glucose transporter 4(GLUT4)gene susceptibility loci and type 2 diabetes mellitus(T2DM)in patients with obstructive sleep apnea-related hypertension.Previous studies have shown that GLUT4 gene polymorphism is associated with OSA hypoxia,and the interaction with fasting blood glucose(>5.6 mmol/L)increases the risk of OSA.Therefore,we aim to investigate the relationship between GLUT4 gene polymorphism loci and glycometabolism disorders by following up of the proportion of new-onset glycometabolism disorders in patients with obstructive sleep apnea-related hypertension,and to provide effective clues for early detection,diagnosis and treatment of glycometabolism disorder in patients with obstructive sleep apnea-related hypertension.Methods We selected 895 hypertensive patients who visited the Hypertensive Center of the People’s Hospital of Xinjiang Uygur Autonomous Region from January to December 2010.All patients completed polysomnography(PSG).According to the exclusion criteria,611 hypertensive patients were included,including 429 OSA patients and 182 non-OSA patients.Four variant loci were found in GLUT4 gene sequencing,and three representative genetic variant loci(rs5417,rs5435,rs5415)were obtained by association analysis.491 hypertensive patients were followed up through the second admission,telephone and face-to-face.Among them,including 249 OSA patients and142 non-OSA patients.The average follow-up time is 4.5 ± 2.4 years.SPSS 22.0statistical software package was used to analyze the relationship between GLUT4 gene polymorphism and hypertension-related sleep apnea.Results1.Baseline data shows that there is a significant difference in fasting blood glucose between the two groups,fasting blood glucose is higher in the OSA group(P=0.044).Among the 491 patients followed up for 4.5 years,there is a significant difference in glycosylated hemoglobin between the two groups(P < 0.001).There are 76 new-onset T2 DM,including 14 in the OSA group and 62 in the non-OSA group.Compared with the two groups,the incidence of T2 DM in the OSA group is significantly higher than that in the non-OSA group(P = 0.028).2.Among 611 subjects,596 are successfully typed at rs5417,593 at rs5415 and 591 at rs5435 in GLUT4 gene.The results show that the recessive model of rs5417 locus have significant difference between the two groups(P < 0.001),but the genotype of rs5417 locus,allele,dominant model,rs5415 locus and rs5435 locus have no significant difference between the two groups.The incidence of T2 DM is compared between the OSA group and the non-OSA group,the results shows that incident T2 DM of rs5417 genotype in GLUT4 SNP5417 increased significantly.3.The interaction between GLUT4 SNPrs5417 CC genotype and LSp O2 < 80% is found to further aggravate the risk of T2 DM.Cox proportional hazard model shows that the risk of T2 DM in OSA patients is twice as high as that in non-OSA patients(HR =2.001,95%CI:1.119-3.578,P = 0.019).Compared with the non-OSA group,the survival freeof T2 DM in the OSA group is lower(log rank test,P = 0.001),which is related to the severity of OSA.The event-free survival rate of OSA patients with CC genotype is significantly reduced,and the cumulative incidence of T2 DM is significantly increased(log rank test,P = 0.0074).The risk of T2 DM in OSA patients with CC genotype is 1.9times higher than that in non-OSA patients with AA + AC genotype(HR: 1.987;95% CI,1.029-3.838;P = 0.041).Conclusions1.OSA patients are more likely to suffer from glycometabolism disorders in hypertensive population,which is twice the risk of T2 DM than non-OSA patients.2.The interaction between GLUT4 SNPrs5417 CC genotype and severe hypoxia further increases the risk of T2 DM.3.CC genotype of GLUT4 SNPrs5417 could increase the risk of new-onset T2 DM. |
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