Association Of The Polymorphism Of AngiotensinⅡ Type 1 Receptor Gene With OSAHS And OSAHS Accompanied By Hypertension

Objectives: To investigate the association of AT1R A1166/C polymorphism with Obstructive Sleep Apnea Hypopn ea Syndrome (OSAHS) and OSAHS accompanied by hypertension(OSAHAHT).And discuss the relativity between the polymorphism and the serious of the Obstructive Sleep Apnea Hypopnea Syndrome(OSAHS) and Obstructive Sleep Apnea Hypopnea Syndrome Accompanied by hypertension (OSAHAHT).The aim is discussing the characteristics between Obstructive Sleep Apnea Syndrome (OSAS) and OSAS a ccompanied by hypertension(OSAHAHT)'s genotype and inves tigate this genotype's operation in the pathogeny and the develo pment of OSAHS and OSAHAHT.Methods: Sixty-five patients (Male 38,Female 27)were selected randomly in the study. All the OSAHS patients were with no cturnal snoring, apnea and excessive daytime sleepiness syndro me. All subjects were sure to be OSAHS by undergoing overnight polysomnography(PSG).All diagnoses were set according to the Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS)'s guide made by China Medical Academy.That is apn ea hypopnea index AHI≥5/h, The AHI was defined as the ave rage of apneic and hypopneic events per sleep hour. Apnea was defined as an absence of airflow for≥10s, and hypopnea was defined as a reduction of airflow associated with a reduction of oxygen saturation by 4% from baseline. The PCR - RFLR was used to test the A1166/C polymorphism of AT1R genes of 65 OSAHS patients with monitoring their multi - lead sleep map, and 70 health people were selected as control. Forty males with OSAHS were included randomly in the study and twenty age-matched and body mass index(BMI)-matched healthy men served as control subjects. OSAHS patients with nocturnal snoring, apnea and excessive daytime sleepiness syndrome and control subjetcs without those syndromes underwent overnight polysomnography(PSG)and portal sleep apnea monitoring, respectively. Inclusion criteria for the present study were apnea-hypopnea index(AHI)≥5/h for OSAHS patients and AHI<5/h for control subjects. Apnea was defined as an absence of airflow for≥10s, and hypopnea was defined as a reduction of airflow associated with a reduction of oxygen saturation by 4% from baseline. The AHI was defined as the average of apneic and hypopneic events per sleep hour. All patients with OSAHS were divided into two subgroups:31 OSAHS patients without complications(age=47.50±10.30, BMI=28.68±3.16kg/m2)and 34 OSAHAHTpatients(age=52.55±12.74,BMI=29.48±3.89kg/m2). All diagnosis according to the Occurrence of hypertension was later than that of OSAHS in patients with OSAHAHT .Other secondary hypertension (such as renovas cular and endocrinic hypertension)were excluded in OSAHAHT patients. 70 health people(Male 40,Female 30) were selected as control group,(age= 47.65±8.07,BMI=27.13±2.14 kg/m2,)There were no significant differences in age and BMI among control subjects and OSAHS and OSAHAHT subjects, OSAHS were excluded in health group by Stardust. Smoking, drinking, diets, drugs and other disturbance factors were excluded in this study. Fasting venous blood were obtained from all observed subjects after sleep-breathing monitoring within the following 5 minutes in the next morning. After that,extract DNA from the blood by using hydroxybenzene-chloroform ,then duplicate the target DNA segment by using polymerase chain reaction,and then test the polymorphism of AT1 genes A1166/C by restriction endonuclease and electrophorety. Chi-square test was used to statistic the distribution of the AA,AC and CC.Group t-test was used to the data of PSG on OSAHS and OSAHSHAT patients.Result: 1.The frequency of AT1R genetype AA, AC, CC were 88.2%,10.3%,1.5% in health people and 72.3%,26.3%,1.4 % in OSAHS patients, The differences were significant (χ2=5.733,P<0.05) .The frequency of allele AandC were 93% and 7%in health people and 85 % and 15 % in OSAHS patients. And also the frequency were significantly different (χ2=4.861,P < 0.05). The frequency of allele A and C were 62% and 38% in OSAHS patients and 80%,20%in OSAHAHT patients. The frequency were significantly different (χ2 = 5 355, P < 0.05).2.In comparing with OSAHS patients and OSAHAHT patients,the frequency of AT1R gengtype AA,AC,CC were 74%,23%,3% in OSAHS patients and 71%,29%,0% in OSAHAHT patients The differ ence were not significantly (χ2=0.105,P>0.05).C omparing with OSAHS patients and OSAHAHT patients,the frequency of all ele-A was much highier than that of C.3. Compared with OSAHS patients, AHI, average arterial oxygen desaturation and average time of apnea were higher in OSAH AHT patients(t=0.7567, 0.54,2.2615 repectively; p<0.0 5),the difference of the lowest SaO2 and time of the arterial oxygen saturation below 90% per apnea/hypopnea (SaO2<90%)were not significant both in OSAHAHT patients and in OSAHS patients (p>0.05).Conclusions: 1.Despite controlling for age, BMI and excluding disturbance factors such as smoking, drinking, diets and drugs, the polymorphism of angiotensinⅡtype 1 receptor gene A1166/C was associated with OSAHS and OSAHAHT.The frequency of gene type AC+CC was much higher than the healthy group.The frequency of allele-1166C were much higher than the health.Comparing with OSAHS patients and OSAHAHT patients,the frequency of AC+CC gene was not significantly different.While the frequency of Allele-1166C was significantly different.It was correlated positively to not only the average time of apnea but also AHI and the percent of SaO2<90% in one night sleep and was not correlated with the lowest SaO2 both in apnea and in Av.desat.Our study showed the frequency of AC+CC genetype and the allele 1166C gene were much higher in patients with OSAHS and OSAHAHT than those in control subjects as well.There were not difference between the frequency of allele gene and genetype in the patients with OSAHS compared with the patients with OSAHAHT.All these showed the genetype of patients with OSAHS have changed in long-time anoxic sleep.This change was correlated positively to the severity of OSAHS and OSAHAHT.The allele A1166/C gene was not only correlated to Hypertension but also a characteric genetype in patients with OSAHS.Our study documents the close correlation between OSAHS and Hypertension farther.