Mitochondrial DNA mutation screening of male patients with obstructive sleep apnea-hypopnea syndrome.

Xiao-Ying Huang,Hong Li,Liang-Xing Wang,Xiao-Mei Xu

doi:10.3892/etm.2014.1748

Abstract

The aim of the present study was to analyze the differences between the genes of the mitochondrial DNA (mtDNA) displacement loop (D-loop) region and the Cambridge Reference sequence, in order to screen the mutation sites and investigate the correlation between mutations, clinical parameters and complications associated with obstructive sleep apnea-hypopnea syndrome (OSAHS). mtDNA was obtained from male patients with OSAHS in the Zhejiang Province. In total, 60 male patients with OSAHS and 102 healthy adults were assessed to determine the levels of fasting blood glucose, total cholesterol, triglyceride (TG) and high-density and low-density lipoproteins (LDL). Furthermore, peripheral mtDNA was extracted and bidirectional sequencing was conducted to enable mutation screening. In the mtDNA D-loop region, 178 mutation sites were identified, of which 115 sites were present in the two groups. The number of non-common sites in the OSAHS group was significantly higher compared with the control group (P<0.05). No statistically significant difference was observed in the mutations among the mild, moderate and severe OSAHS groups (P>0.05). A total of 21 cases in the severe OSAHS group exhibited mutation rates of >10%. In the control group, there were 24 cases where the np73A-G and np263A-G mutations were predominant. The np303–np315 region was identified to be the highly variable region and various mutation forms were observed. Statistically significant differences were observed in the neck perimeter, TG and LDL levels among the OSAHS-no-mutation subgroups (P<0.05) and LDL was shown to be associated with an mtDNA mutation in the OSAHS group. Numerous polymorphic mutation sites were identified in the mtDNA D-loop region of the OSAHS group. Therefore, mtDNA mutation sites may be closely associated with the clinical manifestations and complications of OSAHS.

Highlights

Sleep apnea‐hypopnea syndrome (SAHS) can be divided into three types: Obstructive, central and mixed
obstructive SAHS (OSAHS) has a number of causes and influencing factors, including obesity, hyperlipidemia and hyperglycemia, which are associated with mitochondrial mutations [13,14]
Numerous diseases have been reported to be associated with mutations in the displacement loop (D‐loop) region of mtRNA, and this region is considered to be the OSAHS, obstructive sleep apnea‐hypopnea syndrome; BMI, body mass index; FBG, fasting blood glucose; TC, total cholesterol; TG, triglyceride; HDL, high‐density lipoprotein‐cholesterol; low‐density lipoproteins (LDL), low‐density lipoprotein‐cholesterol

Summary

Introduction

Sleep apnea‐hypopnea syndrome (SAHS) can be divided into three types: Obstructive, central and mixed. Previous studies have identified that the incidence rate of OSAHS in adults is 1‐5% [1] or 41% in a subpopulation of patients with a body mass index (BMI) of >28 kg/m2 [2]. The incidence rate of domestic OSAHS is ~3%. SAHS is an independent risk factor of multiple systemic diseases [3,4] and seriously affects patient health and quality of life. The pathogenesis of SAHS remains unclear, previous studies have demonstrated familial aggregation of OSAHS and genetic predisposition [5]. Patients with OSAHS suffer from recurrent nocturnal intermittent hypoxia, which affects oxidative phosphorylation in the mitochondrial respiratory chain. Hyperlipidemia, hyperglycemia and other pathogenesis factors are closely associated with OSAHS, and may be associated with mitochondrial mutations [6,7]

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