Lack of Association of the APOE ε4 Allele with the Risk of Obstructive Sleep Apnea: Meta-Analysis and Meta-Regression

Thakre, Tushar P; Mamtani, Manju; Kulkarni, Hemant

doi:10.1093/sleep/32.11.1507

Cited by 56 publications

(40 citation statements)

References 33 publications

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“…Our findings, showing the lack of an association of the ACE I/ D genotype with OSA susceptibility, echo the negative results of the recent meta-analyses on the association of ACE I/D genotype with blood pressure [9][10][11]21]. Although the D allele is associated with increased serum ACE activity, the majority of the evidence indicates that the effect of the D allele on blood pressure is small and additional environmental or genetic factors are most likely required to determine blood pressure [5,10,11].…”

Section: Discussionsupporting

confidence: 89%

The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with OSA: a meta-analysis

2011

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Obstructive sleep apnoea (OSA) is an independent risk factor for hypertension. Increased angiotensin-converting enzyme (ACE) activity may be a possible promoting mechanism with different ACE insertion/deletion (I/D) genotypes influencing this activity. Studies investigating the association of ACE I/D polymorphisms with OSA have shown conflicting results. We aimed to undertake a meta-analysis of existing studies exploring the association of ACE I/D polymorphisms with the risk of OSA and hypertension.10 studies were included in a random effects meta-analysis, comprising 1,227 OSA subjects and 1,227 controls.The effect size was measured using the odds ratio. The risk of having OSA in carriers of the D allele was 0.92 (95% CI 0.69-1.23). There was statistically significant heterogeneity across the studies (I 2 542%, p50.08 and I 2 574%, p,0.0001 for genotype and allele frequency, respectively). The association of D allele frequency with the risk of OSA remained nonsignificant after stratification based on ethnicity, source of population sample, and the presence of hypertension. Subgroup analysis failed to show any influence of genotype and allele frequency on OSA severity.This meta-analysis revealed no association between the ACE I/D polymorphisms and OSA susceptibility.KEYWORDS: Angiotensin-converting enzyme polymorphism, meta-analysis, obstructive sleep apnoea O bstructive sleep apnoea (OSA) is characterised by recurrent collapse of the upper airway during sleep, resulting in intermittent hypoxia and sleep fragmentation that can lead to excessive daytime sleepiness. Untreated OSA is an independent risk factor for hypertension [1][2][3]. The exact mechanisms linking OSA and hypertension are not clear. One possibility is that OSA-related hypoxia and arousal might lead to sympathetic hyperactivity and activation of the renin-angiotensin-aldosterone system [4].The angiotensin-converting enzyme (ACE) regulates blood pressure by hydrolysing angiotensin I into angiotensin II and inactivating bradykinin and angiotensin I-VII [5]. The importance of ACE in the regulation of blood pressure is demonstrated by the beneficial effect of ACE inhibitors on hypertension [6]. The insertion/deletion (I/D) polymorphism of ACE has been shown to account for 47% of the observed variance in serum ACE levels. The DD genotype carriers have the highest serum ACE concentrations and II genotype carriers have the lowest serum ACE concentrations [7]. The DD genotype has been associated with hypertension; the association being stronger in Asians and females [8]. However, recent meta-analyses have failed to confirm an association between ACE polymorphisms and hypertension [9][10][11].

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Section: Discussionsupporting

confidence: 89%

The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with OSA: a meta-analysis

2011

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“…Additionally, the metabolic dynamics of E4 differ from those of E3/E4. Furthermore, total cholesterol and LDL cholesterol levels are higher in people with the ε4 allele (15). As APOE is involved in immune response and tissue repair, we can conclude that ε4 has a direct effect on the pathogenesis of AS at the cellular level (16).…”

Section: Discussionmentioning

confidence: 78%

Association of APOE polymorphisms and insulin resistance with TCM syndromes in type 2 diabetes patients with macroangiopathy

Xie

Wang

et al. 2011

Mol Med Report

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Abstract.To investigate the association between apolipoprotein E (APOE) polymorphisms and insulin resistance and Traditional Chinese Medicine (TCM) syndromes in type 2 diabetes mellitus (T2DM) with macroangiopathy, 60 patients with T2DM macroangiopathy were enrolled and divided into three groups: dryness-heat due to deficiency of yin, Qi-Yin deficiency, and Yin-Yang deficiency, according to the TCM syndromes, with a control group of 20 healthy individuals. APOE genotype analysis was performed with polymerase chain reaction amplification and restriction fragment length polymorphism, and the results showed that the proportion of the ε4/4 and ε3/4 genotypes and frequencies of the ε4 and ε3 alleles were higher in the Qi-Yin deficiency group (P<0.05). Among the T2DM macroangiopathy patients, the E4 group had the largest number of cases, as well as a significantly longer disease course compared to the E2 group (P<0.05). The insulin resistance index (IRI), insulin action index and body mass index (BMI) of patients in the Yin-Yang deficiency group were significantly different from those of patients with dryness-heat due to deficiency of yin and Qi-Yin deficiency. Furthermore, correlation analysis of the BMI and IRI of patients in the Yin-Yang deficiency group revealed a correlation coefficient r= 0.696 (P<0.01) and a typical correlation between them. In conclusion, the Qi-Yin deficiency in T2DM patients with macroangiopathy is associated with the APOE E4 and E3 genotypes. Thus, the APOE gene polymorphism can, to some degree, reflect the TCM syndrome types of T2DM patients with macroangiopathy. Insulin resistance plays an important role in the occurrence of T2DM macroangiopathy and is closely associated with the Yin-Yang deficiency according to the TCM differentiating types.

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“…In addition, among patients with the high-risk e4 genotype those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic e4 subjects. Previously, potential links have been observed between APOE genotype and the risk of OSA in some, but not all, studies [26,27]. In addition, some observations suggested a significant effect of APOE genotype on clinical outcomes in terms of cognitive impairment [28] and memory performance in OSA [29], without examining the effects on serum lipids.…”

Section: Discussionmentioning

confidence: 99%

Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea

Tisko

Sopkova

Habalová

et al. 2013

European Respiratory Journal

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There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA.519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography. APOE gene polymorphisms were assessed using real-time PCR.In all APOE genotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in each APOE genotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in e2 carriers and the e3/e3 genotype only. Nevertheless, the e4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk e4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic e4 subjects. APOE genotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p50.009 and p,0.001, respectively; R 2 50.148) and ApoB levels (p50.001 and p50.003, respectively; R 2 50.104). Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried by APOE genotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA. @ERSpublications OSA has adverse effects on several lipid parameters in addition to the effects carried by the APOE genotype

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Lack of Association of the APOE ε4 Allele with the Risk of Obstructive Sleep Apnea: Meta-Analysis and Meta-Regression

Abstract: The hypothesis that the APOE epsilon4 allele may be causally associated with OSA cannot be supported on the basis of published literature.

Cited by 56 publications

References 33 publications

The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with OSA: a meta-analysis

The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with OSA: a meta-analysis

Association of APOE polymorphisms and insulin resistance with TCM syndromes in type 2 diabetes patients with macroangiopathy

Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea

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