Obstructive Sleep Apnea Susceptibility Genes in Chinese Population: A Field Synopsis and Meta-Analysis of Genetic Association Studies

Abstract

BackgroundEpidemiological studies to date have evaluated the association between genetic variants and the susceptibility to obstructive sleep apnea (OSA). However, the results of these studies have been inconclusive. In this current study we performed meta-analysis of genetic association studies (GAS) to pool OSA-susceptible genes in Chinese population, to perform a more precise evaluation of the association.MethodsVarious databases (i.e., PubMed, EMBASE, HuGE Navigator, Wanfang and CNKI) were searched to identify all eligible GAS-related variants associated with susceptibility to OSA. The generalized odds ratio metric (ORG) and the odds ratio (OR) of the allele contrast were used to quantify the impact of genetic variants on the risk of OSA. Cumulative and recursive cumulative meta-analyses (CMA) were also performed to investigate the trend and stability of effect sizes as evidence was accumulated.ResultsThirty-two GAS evaluating 13 polymorphisms in 10 genes were included in our meta-analysis. Significant associations were derived for four polymorphisms either for the allele contrast or for the ORG. The variants TNF-α-308G/A, 5-HTTLPR, 5-HTTVNTR, and APOE showed marginal significance for ORG (95% confidence interval [CI]): 2.01(1.31–3.07); 1.31(1.09–1.58); 1.85(1.16–2.95); 1.79(1.10–2.92); and 1.79(1.10–2.92) respectively. In addition, the TNF-α-308G/A, 5-HTTLPR, and 5-HTTVNTR variants showed significance for the allele contrast: 2.15(1.39–3.31); 2.26(1.58–3.24); 1.32(1.12–1.55); and 1.86(1.12–3.08) respectively. CMA showed a trend towards an association, and recursive CMA indicated that more evidence was needed to determine whether this was significant.ConclusionsTNF-α, 5-HTT, and APOE genes can all be proposed as OSA-susceptibility genes in Chinese population. Genome-wide association studies (GWAS) are therefore urgently needed to confirm our findings within a larger sample of OSA patients in China.

Obstructive sleep apnea and hypertriglyceridaemia share common genetic background: Results of a twin study

“…Respiratory indices were log-transformed to chronic intermittent hypoxia, the expression of PPAR-gamma was found to be decreased (Zhang, Zhang, Li, & Hou, 2017). In humans, polymorphism Pro12Ala of the PPAR-gamma gene was associated with susceptibility to OSA (Sun et al, 2015) and increased risk of hyperlipidaemia in OSA patients in a Chinese population (Chen et al, 2017). Polymorphism of APOE E2 and E4 alleles are linked to higher LDL-cholesterol and lower HDL-cholesterol levels (Kataoka et al, 1996).…”

“…Apart from these, common genetic loci can also contribute to the co-occurrence of OSA and cardiometabolic disease. For instance, polymorphisms of the peroxisome proliferator-activated receptor (PPAR) gamma have been associated with obesity, diabetes (Janani & Ranjitha Kumari, 2015), hyperlipidaemia (Chen et al, 2017) and OSA (Sun, Hu, Tu, Zhong, & Xu, 2015). Polymorphisms of the apolipoprotein E (APOE) gene are linked to dyslipidaemia (Kataoka et al, 1996) as well as OSA (Uyrum et al, 2015;Xu, Qian, Guan, Yi, & Yin, 2015).…”

“…is associated with higher plasma TNF-alpha levels and this polymorphism is a predisposition of OSA (Sun et al, 2015) and hypertension (Ghodsian et al, 2015).…”

Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans

“…OSA affects more than 10% of adults (2) and increases risk of adverse health outcomes, including hypertension and cardiovascular disease as well as increased mortality (3)(4)(5). Candidate gene studies have identified associations between the apnea hypopnea index (AHI), the chief disease defining metric, measured continuously or dichotomized, with variants in genes associated with inflammation, serotoninergic pathways and ventilatory control (6)(7)(8). We have recently identified the first genome-wide significant associations with objectively measured OSA traits (9,10).…”

Etiopathogenesis of obstructive sleep apnoea and its consequences in the children

“…Варианты генов C-реактивного белка (CRP) и IL-6 могут быть связаны с наличием СОАГС в детском возрасте [47]. Исследования демонстрируют корреляцию однонуклеотидных полиморфизов в гене TNF-α и формировании СОАГС [48].…”