葡萄糖转运蛋白4基因多态性与阻塞性睡眠呼吸暂停综合征导致的低氧及相关炎症因子的关系

doi:10.3881/j.issn.1000-503X.2014.04.010

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2014, Vol. 36 ›› Issue (4): 400-409.doi: 10.3881/j.issn.1000-503X.2014.04.010

• Original article • Previous Articles Next Articles

Association of Glucose Transporter 4 Gene Polymorphism with Hypoxia Caused by Obstructive Sleep Apnea Syndrome and with Related Inflammatory Factors

YIN Ting¹,LI Nan-fang²,AI Li-gen²,YAO Xiao-guang²,HONG Jing²,ZHOU Ling²,KONG Jian-qiong²

¹Department of Clinical,Medical College of Shihezi University,Shihezi,Xinjiang 832000,China;²Center of Hypertension of the People’s Hospital of Xinjiang Uygur Autonomous Region,Center of Diagnosis,Treatment,and Research of Hypertension in Xinjiang,Urumqi 830001,China

Received:2014-01-13 Online:2014-08-31 Published:2014-08-31
Contact: LI Nan-fang Tel：0991-8564818,E-mail：lnanfang2010@sina.com
Supported by:
Supported by the National Natural Sciences Foundation of China (81202215) and the Specialized Research Fund for the Doctoral Program of Higher Education (20100001120132)

Abstract

Abstract: Objective To investigate the relationship between genetic polymorphisms of glucose transporter 4 (GLUT4) and hypoxia caused by obstructive sleep apnea syndrome (OSAS) as well as with related inflammatory factors. Methods Consecutive hypertension patients diagnosed at the People’s Hospital of Xinjiang Uygur Autonomous Region were selected from January to December 2010. A total of 859 subjects with possible OSAS base on their histories and physical examination findings udnerwent the polysomnography and inflammatory factor determination,of whom 616 (72%) were diagnosed with moderate and severe hypoxia with OSAS (case group) and 243(28%) without hypoxia or OASA (control group). Ninty-six patients from the case group underwent DNA sequencing at the functional domain of GLUT4 gene to screen for representative mutations. TaqMan PCR was used to genotyping then analyzed the relationship between locis of GLUT4 and hypoxia. Results GLUT4 genome sequencing was performed in 96 severe OSAS patients and 4 mutated sites were found,among which 3 mutated sites (rs5415,rs4517,and rs5435) were selected according to the principle of linkage disequilibrium (r2>0.8) and minimum gene allele frequency >5%. All of single nucleotide polymorphisms (SNP) satisfied Hardy-Weinberg equilibrium (P>0.05). A significant association of GLUT4 SNP rs5417 allele carried in control subjects,compared with moderate and severe hypoxia in OSAS patients (P<0.05)；AA+AC genotype relative to CC with low oxygen levels in subjects significantly reduced. The difference existed in overweight and obese patients,as well as in those aged more than 50 years (P<0.05). AA was still an independent protective factor for hypoxia caused by OSAS (OR=0.385,95%CI=0.210-0.704,P=0.002). Male (OR=1.635,95%CI=1.037-2.577,P=0.034)and total cholesterol(OR=1.600,95%CI=1.287-1.987,P<0.001) were independent risk factors associated with hypoxia. Normal weight(OR=0.059,95%CI=0.037-0.094,P<0.001) and high density lipoprotein cholesterol(OR=0.337,95%CI=0.171-0.666,P=0.002)were independent protective factors for hypoxia. The levels of monocyte chemoattractant protein-1 and C-reaction protein above CC were significantly higher than AA+AC (P<0.05). Conclusion Hypoxia caused by OSAS is associated with GLUT4 gene SNP rs5417.

Key words: glucose transporter 4 gene, polymorphism, hypoxia, obstructive sleep apnea syndrome, inflammatory factors

CLC Number:

R394.5

YIN Ting,LI Nan-fang,AI Li-gen,YAO Xiao-guang,HONG Jing,ZHOU Ling,KONG Jian-qiong. Association of Glucose Transporter 4 Gene Polymorphism with Hypoxia Caused by Obstructive Sleep Apnea Syndrome and with Related Inflammatory Factors[J].Acta Academiae Medicinae Sinica, 2014, 36(4): 400-409.

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