Association Of The Genetic Polymorphisms Of TWIK-related Acid-sensitive K+ Channel-3 With Severe Obstructive Sleep Apnea

Objective Obstructive sleep apnea(OSA)is a common sleep disorder,and such patients have a higher incidence of hypertension.TWIK-related acid-sensitive K+channel-3(TASK-3)was reported to be a risk factor for obstructive sleep apnea(OSA)in animal models.The present study aimed to evaluate the relationship between human TASK-3 gene polymorphisms and obstructive sleep apnea in patients with hypertension,and analyzed its relationship with related sleep parameters.Methods The study was consecutively selected from April 2016 to December 2016 for patients with suspected obstructive sleep apnea who were over 18 years old in the Hypertension Clinical Research Center of the People’s Hospital of Xinjiang Autonomous Region.All patients completed polysomnography(PSG),according to Excluding the standard and OSA diagnostic criteria,a total of 332 patients were included,of which 170 subjects without OSA and 162 subjects with severe OSA.Three single nucleotide polymorphisms(rs2615374,rs3808403 and rs888345)of TASK-3gene were selected as representative loci,according to principle of linkage disequilibrium(r2>0.8)and minimum allele frequency(MAF)> 5%.We collected the demographic and laboratory test indicators of the experimental group and the control group,and collected peripheral blood to extract genomic DNA.The genotypes of the above polymorphisms was performed by Kompetitive Allele Specifc PCR.Using SPSS19.0 analyzed the relationship between TASK-3 gene polymorphism and severe OSA.Results1.The significant differences in additive models(P=0.047),alleles(P=0.014)and dominant model(P=0.020)of rs2615374 were observed between severe and non OSA subjects.The distributions of additive models(P=0.005)and dominant model(P=0.015)of rs3808403 were also significantly different between two groups.CT+TT genotype of rs3808403 was considered as risk factors for severe OSA(CT+TT: [OR] = 2.09,95%CI:1.13-3.88,P=0.019).In addition,we found that both the GA+AA genotype of rs2615374 and the CT+TT genotype of rs3808403 had higher triglyceride levels.2.We found in different body mass index people,body mass index< 28Kg/m2,the dominant model of rs2615374(P = 0.021)was different between severe OSA and non-OSA subjects.When body mass index ≥ 28Kg/m2,additive model(P < 0.001;P =0.029),the allele model(P = 0.020;P = 0.050)and the dominant model(P < 0.001;P =0.012)of rs3808403 and rs888345 were also significantly different between the two groups.After adjusting for confounding factors,Logistic regression analysis showed that the rs3808403(TT+CT)and rs888345(CC+CT)in body mass index≥ 28Kg/m2 were potential risk factors for severe OSA.In addition,similar differences were observed between the dominant model of the TASK-3 gene SNPs and the severe OSA parameters when body mass index was grouped by 28kg/m2.conclusions1.Our study suggested that the polymorphisms of rs3808403 in TASK-3 gene were associated with severe OSA,and CT+TT genotype of rs3808403 locus was a risk factor for severe OSA among the total population.2.The CT+TT genotype of rs3808403 and the CC+CT genotype of rs888345 in obese people may be potential risk factors for severe OSA.