[GG Genotype at rs1275988 and rs2586886 Loci of TWIK-related Acid-sensitive K + Channel-1 Gene is A Potential Risk Factor for Severe Obstructive Sleep Apnea].

Objective To explore the mechanism of obstructive sleep apnea(OSA) by assessing the association between human TWIK-related acid-sensitive K + channel-1(TASK-1) gene and OSA. Methods A total of 164 patients with severe OSA and 171 patients without OSA were recruited from the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region,China,from April to December 2016.Two single nucleotide polymorphisms(rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a Kompetitive Allele Specific PCR genotyping system. Results In patients with blood potassium <3.95 mmol/L,the distribution of rs1275988 alleles(G vs.A)(χ 2=4.474,P=0.034) and recessive model(GG+GA vs.AA)(χ 2=4.327,P=0.038) showed significant differences between severe and non-OSA groups.The distribution of rs2586886 alleles(G vs.A)(χ 2=6.345,P=0.012) and dominant model(AA+GA vs.GA)(χ 2=4.431,P=0.035) showed significant differences between severe and non-OSA groups.The Logistic regression analysis showed that the GG genotype was a risk factor for OSA patients with blood potassium <3.95 mmol/L(OR=7.854,95% CI:1.710-36.000,P=0.008;OR=8.849,95% CI:1.816-43.117,P=0.007). Conclusions Both the GG genotypes of rs1275988 and rs2586886 in the TASK-1 gene may be potential risk factors in severe OSA patients with blood potassium <3.95 mmol/L.Serum potassium>3.95 mmol/L in patients with TASK-1 GG genotype may be conducive to reducing the incidence of severe OSA.

[TWIK-related Acid Sensitive K + Channels in the Regulation of Respiration and Sleep].

TWIK-related acid-sensitive K + channel(TASK)is an important member of the two-pore-domain potassium channels family. It is widely expressed in the central nervous system and peripheral tissues and is extremely sensitive to hypoxia and pH changes in extracellular fluid. TASK participates in regulating the expression of respiratory center and the respiratory movement and also plays certain role in sleep regulation. This article reviews the recent advances in the roles of TASK in the regulation of respiration and sleep.

Genetic variations in the KCNJ5 gene in primary aldosteronism patients from Xinjiang, China.

BACKGROUND: Primary aldosteronism (PA) is the most common endocrine form of secondary hypertension, and one of the most common subtypes of sporadic PA is aldosterone-producing adenoma (APA). Recently, two somatic mutations of the KCNJ5 gene were implicated in APA, and two germline mutations were associated with familial hyperaldosteronism III. OBJECTIVES: This case-control study was designed to investigate the relationship between genetic variations in the KCNJ5 gene and sporadic PA patients in Xinjiang, China. METHODS: Five common single nucleotide polymorphisms (SNPs) of the KCNJ5 gene (rs6590357, rs4937391, rs3740835, rs2604204, and rs11221497) were detected in patients with sporadic PA (n = 235) and essential hypertension (EH; n=913) by the TaqMan polymerase chain reaction method. RESULTS: The EH group and the PA group showed significant differences in the distributions of genotypes and alleles of rs4937391 and rs2604204 in total and male subjects (P<0.05), as well as rs3740835 in male subjects (P<0.05). However, only the association between the rs2604204 genotype and male sporadic PA remained significant after Bonferroni's correction (P<0.01). Furthermore, logistic regression analysis demonstrated that the CC genotype of rs2604204 was a risk factor for male patients with sporadic PA, after adjusting for age and body mass index (odds ratio=2.228, 95% CI: 1.300-3.819, P=0.004). CONCLUSION: The genetic variant rs2604204 of KCNJ5 is associated with sporadic PA in Chinese males, suggesting that KCNJ5 may be involved in the pathogenesis of sporadic PA in these particular patients.

[Relationship between the G protein gated inward rectifier potassium channel 4 gene polymorphism and dyslipidemia of Uyghur residents].

OBJECTIVE: To investigate the relationship between the G protein-gated inward rectifier K+ channel subunit 4 (GIRK4) gene polymorphism and the dyslipidemia among Uyghur residents in Xinjiang. METHODS: The polymorphisms of rs2604204, rs4937391, rs6590357, and rs11221497 among the Uyghur residents were genotyped using Taqman polymerase chain reaction (PCR). Lipid levels were measured by conventional methods and were analyzed. RESULTS: In the less-than-50-years population, the genotype distributions of the rs6590357 was statistically significant different in subjects with or without abnormal triglycerides (P=0.005). Aslo, the the genotype distributions of the rs11221497 also significantly differed in subjects with normal compared or abnormal TG (P=0.011). Logistic regression analysis suggested that rs6590357 still had positive association with TG abnormalities in subjects under 50 years (P=0.014). rs11221497 also had positive association with TC abnormalities. The TG levels of CT+TT genotypes were significantly higher than the CC group (P=0.006). Haplotype analysis found that the differences of H3 haplotype frequencies between the TG abnormal and normal groups were statistically significant (P=0.007). CONCLUSION: The polymorphisms of rs11221497 and rs6590357 of GIRK4 gene may play a role in the development of dyslipidemia in Uygur population.

[Association between GIRK4 gene polymorphisms and insulin resistance in Xinjiang Uygur population].

OBJECTIVE: To assess the association between polymorphisms of protein-activated inwardly rectifying K+ channel (GIRK4) gene and insulin resistance (IR) in Xinjiang Uygur population. METHODS: A cross-sectional epidemiological survey-based case-control study was carried out, for which 1295 subjects (including 324 IR patients and 971 non-IR controls) were randomly selected. Functional region of the GIRK4 gene was sequenced for 48 randomly selected IR patients. Representative variable sites were chosen, with its association with IR assessed in 1295 Uygur subjects. RESULTS: rs11221497 variant was associated with IR in Uygur subjects under 50 years old (P=0.017 in genotype model, P=0.009 in dominant model). Subjects with dominant model of CC genotype have an OR of 1.833 (95%CI: 1.157-2.905) for IR. CONCLUSION: GIRK4 gene polymorphisms may be associated with IR in Uygur ethnics from Xinjiang. The CC genotype of rs11221497 variant is a risk factor for IR.

[Epidemiological survey of lipid levels and factors in Kazakan people over 30-year old in Fukang of Xinjiang].

OBJECTIVE: To study the lipids level in Kazakan individuals over 30-year-old in Fukang area of Xinjiang. METHODS: Random cluster multistage sampling method were performed to select the subjects, and 991 individuals aged older than 30 from Fukang of Xinjiang were included. The plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), plasma glucose and insulin were measured. Related adverse cardiovascular risk factors were discussed. RESULTS: The mean plasma TC, TG, HDL-C and LDL-C of Kazakan residents over 30-year-old in Fukang of Xinjiang were (5.05 ± 1.07), (1.10 ± 0.66), (1.46 ± 0.38) and (3.06 ± 0.84) mmol/L, respectively. TC, TG and LDL-C levels in male subjects were higher than those in females (male vs female: TC: (5.19 ± 1.05) mmol/L vs (4.94 ± 1.07) mmol/L, t = 3.57, P < 0.01; TG: (1.32 ± 0.80) mmol/L vs (0.94 ± 0.46) mmol/L, t = 8.63, P < 0.01; LDL-C: (3.30 ± 0.85) mmol/L vs (2.88 ± 0.79) mmol/L, t = 8.06, P < 0.01). While the HDL-C level in male subjects was lower than that of female (male vs female: (1.32 ± 0.33) mmol/L vs (1.57 ± 0.38) mmol/L, t = 11.48, P < 0.01). The prevalence of dyslipidemia was 28.3% (280/991) in the overall populations. In the overall populations, the prevalence of hypercholesteremia, hypertriglyceridemia, high low-density lipoprotein cholesterolemia and low serum high density lipoprotein cholesterolemia were 12.6% (125/991), 6.6% (65/991), 11.0% (109/991) and 10.1% (100/991), respectively. The prevalence of individuals with borderline-high TC, TG and LDL-C were 27.0% (268/991), 7.6% (75/991) and 20.5% (203/991), respectively. The prevalence of dyslipidemia was 40.0% (172/430) in male populations. The prevalence of dyslipidemia in group aged 30 - 39, 40 - 49, 50 - 59, 60 and above were 26.2% (78/298), 26.0% (91/350), 31.2% (73/234) and 34.9% (38/109), respectively, the trend of prevalence was significant by trend test for groups comparison (χ(2) = 3.94, P < 0.05). Adjusting for age and gender, TG was positively correlated with waist circumference, abdominal circumference and BMI, the partial relation coefficients were 0.368 (P < 0.01), 0.336 (P < 0.01) and 0.331 (P < 0.01), respectively, and HDL-C was negatively correlated with waist circumference, abdominal circumference and BMI, the partial relation coefficients were -0.340 (P < 0.01), -0.339 (P < 0.01) and -0.321 (P < 0.01), respectively. CONCLUSION: The lipid levels of Kazakan residents from Fukang area are high and are characterized by hypercholesteremia and high low-density lipoprotein cholesterolemia, and more attention of the prevention of dyslipidemia in this populations should be paid to males, border-line abnormal and those aged over 60-year old.

Detection of genetic variations of regulator of G-protein signaling 2 in hypertensives by sequencing / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the new genetic variations of regulator of G-protein signalling 2 (RGS2) gene in Kazakh hypertensives.</p><p><b>METHODS</b>Totally 94 Kazakh patients with essential hypertension were enrolled and genomic DNA was extracted from their peripheral blood leukocytes. All the exon regions and their flanking sequences of RGS2 were directly sequenced.</p><p><b>RESULTS</b>We identified 13 variants including 5 common- single nucleotide polymorphisms with a minor allele frequency over 5%single nucleotide polymorphisms and 8 novel variations in 94 Kazakh hypertensives. Among these variations, 2 were in the introns and 7 in the promoter region. One subject had a G-to-C substitution at nucleotide 54 in exon 1, which lead to an amino acid substitution from K-to-N at position 18; another individual had an A-to-G substitution at nucleotide 2422 in exon 5, resulting in an amino acid from Y-to-C at position 178. Among eight common single nucleotide polymorphisms, -638A>G, -395G>C, 1891-1892TC I/D, and 2971G>C,and -43A>T and 2297A>G were in tight linkage disequilibrium with an r-square of more than 0.8, respectively.</p><p><b>CONCLUSIONS</b>The variants and their frequencies in RGS2 gene in Kazakh hypertensives may have ethnic differences when compared with other populations. The frequencies of the mutations are low in this population, and whether they influence blood pressure regulation requires further functional experiments.</p>

[Etiology analysis for hospitalized hypertensive patients: 10 years report from the department of hypertension (1999 - 2008)].

OBJECTIVE: To analyze etiology of hospitalized hypertensive patients in the department of hypertension from 1999 to 2008. METHODS: This retrospective study was performed to analyze the etiology of hospitalized hypertensive patients in department of hypertension and to show the distribution change of hypertension from 1999 to 2008. RESULTS: (1) There were 5867 (75.1%) patients with essential hypertension and 1942 (24.9%) patients with secondary hypertension (SH). (2) The prevalence rate of SH increased significantly during the 10 years (χ(2) = 387.621, P < 0.001) and was higher in 2008 than in 1999 (39.3% vs. 9.5%, P < 0.05). The prevalence of obstructive sleep apnea syndrome (OSAS) and primary aldosteronism (PA) in 2008 increased 38.3 and 1.8 times respectively than in 1999 (χ(2) = 304.025, P < 0.001; χ(2) = 42.845, P < 0.001) and other SH remained unchanged. (3) The prevalence of PA complicated with OSAS increased significantly in recent five years (χ(2) = 26.376, P < 0.001). Incidence of OSAS was 23.9% in PA patients and incidence of PA was 6.7% in OSAS patients. CONCLUSIONS: With the insights gained on hypertension mechanism and the development of new diagnostic technology, percent of diagnosed SH increased remarkably in recent years in hospitalized hypertensive patients in our department of hypertension. OSAS and PA are the leading causes of SH.

[Etiology analysis of 628 patients with refractory hypertension].

OBJECTIVE: To analyze the etiology of 628 patients with refractory hypertension and to observe the disease distribution with respect to gender and different age groups. METHODS: In this study, clinical data of 628 refractory hypertensives who hospitalized in our hospital from September 1997 to December 2005 were retrospectively analyzed. RESULTS: (1) There were 80.1% (503/628) patients with essential hypertension, 18.9% (119/628) with secondary hypertension (SH) while diagnosis was not clear in 1.0% (6/628) patients. Renovascular hypertension (33.6%) and obstructive sleep apnea syndrome (23.5%) were the major causes of SH. The highest prevalence rate of endocrine hypertension was primary aldosteronism (13.5%). (2) There were significantly more male patients than female patients with essential hypertension, SH, renal hypertension, obstructive sleep apnea syndrome, primary aldosteronism while the incidence of pheochromocytoma in female was significantly higher than that in male patients (all P < 0.05). The incidence of renovascular hypertension was similar between male and female patients. (3) SH occurred more often in young patients (33.1%) than in aged patients (13.8%, P < 0.05). CONCLUSION: Our data from this patient cohort showed that SH, especially renovascular hypertension and obstructive sleep apnea syndrome are major causes for refractory hypertension in young patients and primary aldosteronism was the commonest reason of endocrine hypertension in youth and middle-aged patients with refractory hypertension.

[The relationship between dyslipemia and the polymorphism of angiotensin II type 1 receptor gene in hypertensive Kazakans of Xinjiang.].

OBJECTIVE: To investigate the relationship between dyslipidemia and the polymorphism of angiotensin II type 1 receptor (AT(1)R) gene A1166C in hypertensive Kazakans of Xinjiang area. METHODS: Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) methods were used to detect the A1166C polymorphism of AT(1)R gene of 296 hypertensive and 198 normotensive Kazakans. Biochemical parameters were measured by autochemical emalyzer. RESULTS: (1) The TC and LDL-C levels are significantly higher in hypertension group than those in normotensive controls [TC: (4.91 +/- 1.19) mmol/L vs. (4.43 +/- 1.20) mmol/L; LDL-C: (3.36 +/- 1.01) mmol/L vs. (2.94 +/- 1.30) mmol/L, P < 0.001). (2) In hypertension group, TC and LDL-C are related to A1166C polymorphism of AT(1)R gene and TC and LDL-C of AC carriers are significantly higher than AA carriers (P < 0.05). CONCLUSION: The dyslipidemia is related to A1166C polymorphism of AT(1)R gene in hypertensive Kazakans.

[Comparison of low density lipoprotein cholesterol levels in Kazaks and Mongolians from Xinjiang pastoral area].

OBJECTIVE: To compare the serum levels of low density lipoprotein cholesterol in Kazaks and Mongolians from Xinjiang pastoral area. METHODS: A randomized cluster sampling was performed to obtain a representative sample of population in Xinjiang Hefeng pastoral area. Blood was taken from 632 individuals aged 30 and older for measurements of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) by automatic biochemical analyzer. The serum levels of low density lipoprotein cholesterol (LDL-C) was calculated according to the formula. RESULTS: The mean serum level of LDL-C was significantly higher in Kazaks [(3.68 +/- 1.16) mmol/L] than that in Mongolians [(3.29 +/- 1.23) mmol/L, P < 0.001]. The serum levels of LDL-C in Kazaks were significantly associated with mean artery pressure. The serum levels of LDL-C in Mongolians were significantly associated with body mass index. CONCLUSION: The serum levels of LDL-C were higher in Kazaks compared that in Mongolians in Xinjiang pastoral area.

[Analysis of etiology of the patients with hypertension from the People's Hospital of Xinjiang Uygur Autonomous Region].

OBJECTIVE: To analyze the etiology of the patients with hypertension from the People's Hospital of Xinjiang Uigur Autonomous Region, and to investigate the distribution of hypertension in gender and different ages. METHODS: From September 1997 to December 2005, the data of 4642 patients with hypertension was retrospective studied. RESULTS: (1) Of all the patients, 85.24% were essential hypertension (EH) and 14.76% were secondary hypertension (SH). Higher prevalence of sleep apnea syndrome (42.92%) and anxiety (15.04%) was found in secondary hypertension. The highest prevalence of primary aldosteronism (12.12%) was found in endocrine hypertension. (2) The male patients with hypertension were more than the female ones, and the incidence of EH, sleep apnea syndrome (SAS) and primary aldosteronism was higher in male patients than female ones, and the following was less than female: anxiety, pheochromocytoma and renovascular hypertension. (3) Among the patients with SH, 21.9% were found in youth, and 9.85% in aged. CONCLUSION: For the young, SH should be excluded, especially SAS and anxiety should be screened and differentiated. The highest prevalence of endocrine hypertension is primary aldosteronism in young and middle-aged male. The prevalence of pheochromocytoma in female is higher than that of male.

[The relationship between the beta-2-adrenergic receptor gene +46 Arg 16/Gly variant and serum level of low density lipoprotein-cholesterol in Kazakans of Xinjiang].

OBJECTIVE: To investigate the distribution of beta-2-AR +46 A-->G variant in Kazakans of Xinjiang and the relationship of the variant with low density lipoprotein-cholesterol (LDL-C) level in this population. METHODS: The genotypes of beta-2-AR gene Arg16/Gly variant were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique in 506 Kazakans with age from 30 to 69, and its distribution and relationship to LDL-C level were investigated. RESULTS: (1) The frequencies of genotypes AA, AG, GG and alleles A, G of beta-2-AR +46 variant in this population were 0.310, 0.455, 0.235 and 0.538, 0.462 respectively, which were accorded with Hardy-Weinberg equilibrium. (2) The Gly16/Gly genotype had highest LDL-C level in the three genotypes, and were significantly higher than Arg16/Gly genotype (P < 0.05). (3) Comparing the effect of beta-2-AR gene +46 variant on serum lipid in males with females, we found that females with Gly16/Gly genotype had the highest level of serum LDL-C. CONCLUSIONS: These data show that Gly16/Gly genotype of beta-2-AR gene +46 A-->G variant is associated with higher level of serum LDL-C in this population, especially in female.

[The relationship between the variants in 5' upstream core promoter A(-6)G and A(-20)C of angiotensinogen gene and essential hypertension in Kazakans of Xinjiang].

OBJECTIVE: To investigate whether the variants A(-6)G and A(-20)C of angiotensinogen (AGT) gene are involved in the pathogenesis of essential hypertension in Kazakans. METHODS: T his case control study recruited 125 subjects with hypertension and 74 normotensive subjects from Kazakans of Xinjiang. Genomic DNA from leukocytes was analyzed for genetic variants A(-6)G and A(-20)C in 5' upstream core promoter of AGT gene by polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), restriction fragment length polymorphism (RFLP) and automatic sequencing. RESULTS: (1)There were only A(-6)G and A(-20)C variants in the -164 to +73 region of Kazakans' AGT gene. (2) The distributions of genotypes AA, AG, GG at locus -6 of AGT gene showed significant difference between the hypertensive group (0.39, 0.45, 0.16) and the normotensive group (0.49, 0.49, 0.02; Chi2=8.56, P=0.014). There were evident differences in the frequencies of the -6A and the -6G allele of the two groups (0.62, 0.38 and 0.73, 0.27; Chi2=5.35, P=0.021). (3) No significant difference was observed in the distribution of genotypes AA, AC, CC at locus -20 of AGT gene between the hypertensive group (0.69, 0.26, 0.05) and the normotensive group (0.65, 0.32, 0.03; Chi2=2.42, P=0.30). There was no distinct difference in the frequencies of the -20A allele and the -20C allele of the two groups (0.82, 0.18 and 0.82, 0.18; Chi2=0, P=0.99). (4) No significant difference was found at the levels of systolic and diastolic blood pressure between the groups corresponding to genotypes at the loci -6 and -20 of AGT gene. CONCLUSION: The results suggest that the polymorphism of A(-6)G in 5' upstream core promoter of the AGT gene may be involved in the pathogenesis of essential hypertension in Kazakans, while the A(-20)C variant may not play an important role in the etiology of essential hypertension in Kazakans.