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 / 中国医学科学院学报

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. 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. In patients with blood potassium 3.95 mmol/L in patients with TASK-1 GG genotype may be conducive to reducing the incidence of severe OSA.

Genetic variants of rs1275988 and rs2586886 in TWIK-related acidsensitive K+ channel-1 gene may be potential risk factors for obese patients with obstructive sleep apnea / 中华医学杂志(英文版)

Background@#The pathogenesis of obstructive sleep apnea (OSA) remains not fully understood. This study aimed to explore the mechanism of OSA by assessing the association between the human tandem of P domains in a weak inwardly rectifying K+ channel (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 Center for Hypertension of People’s Hospital of Xinjiang Uygur Autonomous Region (China) from April to December in 2016. Two single nucleotide polymorphisms (rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a kompetitive allele specific polymerase chain reaction genotyping system. Clinical-pathological characteristics and genotype data were compared between the severe and non-OSA groups to explore the association between TASK-1 gene polymorphism and severe OSA.@*Results@#There were no significant differences in genotype distribution, allele frequency, and the recessive and dominant model of the two selected single nucleotide polymorphisms (rs1275988 and rs2586886) between the severe and non-OSA groups in the total population (P < 0.05). However, for patients with a body mass index (BMI) ≥28 kg/m2, the distribution of genotypes and alleles, and the recessive model (GG + GA vs. AA) exhibited significant differences between the severe and non-OSA group (for genotypes: P = 0.014 and P = 0.026; for alleles: P = 0.006 and P = 0.011; for the recessive model: P = 0.005 and P = 0.009, respectively). The simple logistic regression analysis revealed that the GG genotype was a risk factor for OSA. The odds ratio (OR) and 95% confidence intervals (CI) were 4.902 (1.582–15.186, P = 0.006) for rs1275988 and 4.420 (1.422–13.734, P = 0.010) for rs2586886, respectively. In multivariate logistic regression analysis, the combination of GG genotypes of rs1275988 with BMI ≥28 kg/m2 increased the risk of severe OSA (OR = 8.916, 95% CI 4.506–17.645, P < 0.001).@*Conclusion@#Both the GG genotype of rs1275988 and GG genotype of rs2586886 in the TASK-1 gene may play as potential risk factors in obese patients with OSA.

Genetic variants of rs1275988 and rs2586886 in TWIK-related acid-sensitive K+ channel-1 gene may be potential risk factors for obese patients with obstructive sleep apnea / 中华医学杂志(英文版)

BACKGROUND@#The pathogenesis of obstructive sleep apnea (OSA) remains not fully understood. This study aimed to explore the mechanism of OSA by assessing the association between the human tandem of P domains in a weak inwardly rectifying K channel (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 Center for Hypertension of People's Hospital of Xinjiang Uygur Autonomous Region (China) from April to December in 2016. Two single nucleotide polymorphisms (rs1275988 and rs2586886) in the TASK-1 gene were selected and genotyped using a kompetitive allele specific polymerase chain reaction genotyping system. Clinical-pathological characteristics and genotype data were compared between the severe and non-OSA groups to explore the association between TASK-1 gene polymorphism and severe OSA.@*RESULTS@#There were no significant differences in genotype distribution, allele frequency, and the recessive and dominant model of the two selected single nucleotide polymorphisms (rs1275988 and rs2586886) between the severe and non-OSA groups in the total population (P > 0.05). However, for patients with a body mass index (BMI) ≥28 kg/m, the distribution of genotypes and alleles, and the recessive model (GG + GA vs. AA) exhibited significant differences between the severe and non-OSA group (for genotypes: P = 0.014 and P = 0.026; for alleles: P = 0.006 and P = 0.011; for the recessive model: P = 0.005 and P = 0.009, respectively). The simple logistic regression analysis revealed that the GG genotype was a risk factor for OSA. The odds ratio (OR) and 95% confidence intervals (CI) were 4.902 (1.582-15.186, P = 0.006) for rs1275988 and 4.420 (1.422-13.734, P = 0.010) for rs2586886, respectively. In multivariate logistic regression analysis, the combination of GG genotypes of rs1275988 with BMI ≥28 kg/m increased the risk of severe OSA (OR = 8.916, 95% CI 4.506-17.645, P < 0.001).@*CONCLUSION@#Both the GG genotype of rs1275988 and GG genotype of rs2586886 in the TASK-1 gene may play as potential risk factors in obese patients with OSA.

TWIK-related Acid Sensitive K Channels in the Regulation of Respiration and Sleep / 中国医学科学院学报

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.

Relationship between female dyslipidemia and polymorphism of suppressor of cytokine signaling-3 in Xinjiang Uygur population / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore whether the polymorphism of suppressor of cytokine signaling-3 (SOCS-3) and dyslipidemia are correlated in Uygur females.</p><p><b>METHODS</b>A total of 1379 Uygur females from Xinjiang Uygur Autonomous Region were enrolled in this study. Three single nucleotide polymorphisms (SNPs), namely rs12953258, rs4969168, and rs9914220, were analyzed after being genotyped.</p><p><b>RESULTS</b>Of these three SNPs, the frequency distribution of rs12953258 sites was found to be significantly different between dyslipidemia group and normal group (P=0.032). The frequency distribution of rs12953258 sites between the high-density lipoprotein-cholesterol (HDL-C) abnormal group and normal group also showed significant difference (P=0.029). Logistic regression analysis showed that the genotype AA of rs12953258 was a risk factor for dyslipidemia among the Uygur females [CC vs. AA:OR=3.271,95%CI(1.092-9.797), P=0.034]. The genotype AA of rs12953258 might be related to the decreased high HDL-C and increased trigleceride, whereas the genotype AA coupled with abnormal body mass index (BMI) were more likely to be linked with the higher prevalence of dyslipidemia in Uygur females.</p><p><b>CONCLUSIONS</b>The polymorphism of SOCS-3 is correlated to the dyslipidemia in Uygur females in Xinjiang. Carriers of Genotype AA of rs12953258 coupled with abnormal BMI are more susceptible to dyslipidemia.</p>

Association of glucose transporter 4 gene polymorphism with hypoxia caused by obstructive sleep apnea syndrome and with related inflammatory factors / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationship between genetic polymorphisms of glucose transporter 4 (GLUT4) and hypoxia caused by obstructive sleep apnea syndrome (OSAS) as well as with related inflammatory factors.</p><p><b>METHODS</b>Consecutive hypertension patients diagnosed at the People's Hospital of Xinjiang Uygur Autonomous Region were selected from January to December 2010. A total of 859 subjects with possible OSAS base on their histories and physical examination findings udner went the polysomnography and inflammatory factor determination, of whom 616 (72%) were diagnosed with moderate and severe hypoxia with OSAS (case group) and 243 (28%) without hypoxia or OASA (control group). Ninty-six patients from the case group underwent DNA sequencing at the functional domain of GLUT4 gene to screen for representative mutations. TaqMan PCR was used to genotyping then analyzed the relationship between locis of GLUT4 and hypoxia.</p><p><b>RESULTS</b>GLUT4 genome sequencing was performed in 96 severe OSAS patients and 4 mutated sites were found, among which 3 mutated sites (rs5415, rs4517, and rs5435) were selected according to the principle of linkage disequilibrium (r² > 0.8) and minimum gene allele frequency > 5%. All of single nucleotide polymorphisms (SNP) satisfied Hardy-Weinberg equilibrium (P>0.05). A significant association of GLUT4 SNP rs5417 allele carried in control subjects, compared with moderate and severe hypoxia in OSAS patients (P<0.05); AA+AC genotype relative to CC with low oxygen levels in subjects significantly reduced. The difference existed in overweight and obese patients, as well as in those aged more than 50 years (P<0.05). AA was still an independent protective factor for hypoxia caused by OSAS (OR=0.385, 95%CI = 0.210-0.704, P=0.002). Male (OR=1.635, 95% CI=1.037-2.577, P=0.034) and total cholesterol (OR=1.600, 95% CI=1.287-1.987, P<0.001) were independent risk factors associated with hypoxia. Normal weight(OR=0.059, 95% CI=0.037-0.094, P<0.001) and high density lipoprotein cholesterol (OR=0.337, 95% CI=0.171-0.666, P=0.002)were independent protective factors for hypoxia. The levels of monocyte chemoattractant protein-1 and C-reaction protein above CC were significantly higher than AA+AC (P<0.05).</p><p><b>CONCLUSION</b>Hypoxia caused by OSAS is associated with GLUT4 gene SNP rs5417.</p>

Association of interleukin-1β genetic polymorphisms with obstructive sleep apnea syndrome / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the association between interleukin (IL)-1β genetic polymorphisms and obstructive sleep apnea syndrome (OSAS).</p><p><b>METHODS</b>Totally 850 individuals with hypertension were included. All of them were checked by polysomnography in the Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from January to December in 2010. According to the results of polysomnography, these subjects were divided into non-OSAS group (n=225)and OSAS group (n=625). Genetic variations were sequenced and screened at loci over functional region of IL-1β gene in 96 patients with severe OSAS.The typical loci were selected for genotyping by TaqMan-polymerase chain reaction in 850 subjects.</p><p><b>RESULTS</b>One novel and 5 known variations in the IL-1β gene were identified, and then three representative mutation loci were selected for genotyping.The allele frequency distribution of rs1143633 was significantly different between the OSAS and non-OSAS groups in the total and male populations (χ(2)=9.258, P=0.002;χ(2)=5.119, P=0.024, respectively). Although the parameters of sleep apnea monitoring showed no significant difference in individuals with CC, CT, and TT genotypes of rs1143633 in total, male, and female populations (P>0.05), the median of the apnea hypopnea index of CT genotype was significantly higher than that of CC and TT in total and male populations and the mean of the lowest blood oxygen saturation increased in individuals with CC, CT, and TT genotypes of rs1143633 in total and male populations.Haplotype was no significantly associated with OSAS in total,male,and female populations(P>0.05).Logistic regression analysis showed that CT genotype of rs1143633 variation was a risk factor for OSAS in total and male populations (OR=1.574,95% CI=1.061-2.437,P=0.042;OR=1.887,95% CI=1.091- 3.265,P=0.023).</p><p><b>CONCLUSION</b>The rs1143633 polymorphism in IL-1β gene may be associated with OSAS.</p>

Association of MK2 gene polymorphisms with low-density lipoprotein cholesterol and tumor necrosis factor-alpha in Uygur population from Hetian area of Xinjiang / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the association of MK2 gene with low density lipoprotein cholesterol (LDL-C) and tumor necrosis factor-alpha (TNF-Α) between different gender in Xinjiang Uygur population.</p><p><b>METHODS</b>A total of 350 Uygur males and 595 females were recruited randomly from Hetian area. Two single nucleotide polymorphisms (44890c/t, rs 45514798) in MK2 gene were selected and genotyped by Taqman-PCR in these subjects. All subjects underwent questionnaire-based survey, physical examination, measurement of lipid profiles and plasma TNF-Α determination.</p><p><b>RESULTS</b>Among the male subjects, the concentration of total cholesterol (TC) [TT vs. CT vs. CC: (4.35±1.20) mmol/L vs. (4.69±1.34) mmol/L vs. (4.83±1.44) mmol/L, P=0.033]and TNF-Α [TT vs.CT vs.CC: (106.63±62.39) ng/dL vs. (128.44±86.15) ng/dL vs. (153.06±82.99) ng/dL, P=0.001]were significantly different in 3 genotypes of 44890c/t. However, the LDL-C levels in TT, CT, and CC genotypes of 44890c/t were not different neither in males nor in females [males: (2.64±1.16) mmol/L vs. (2.81±1.28) mmol/L vs. (3.04±1.32) mmol/L, P>0.05; females: (2.42±1.11) mmol/L vs. (2.36±0.99) mmol/L vs. (2.43±1.05) mmol/L, P>0.05]. None of the allele and genotype frequencies of 44890c/tand rs 45514798 were different between high LDL-C group and control group. Linear regression analysis indicated that body mass index (BMI) (beta=0.089) and TNF-Α (beta=0.092) were significantly associated with LDL-C levels in males (P<0.05), while the age, BMI, and waist/hip ratio with LDL-C levels in females (P<0.05).</p><p><b>CONCLUSION</b>The nucleotide polymorphisms (44890c/t and rs 45514798) in MK2 gene may not be associated with LDL-C in both males and females in the Uygur population in Hetian, Xinjiang.</p>

Association study of PRDM16 gene polymorphisms with essential hypertension in Xinjiang Uygur population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of polymorphisms of PR domain containing 16 gene (PRDM16) with essential hypertension in ethnic Uygur population from Xinjiang, China.</p><p><b>METHODS</b>Functional regions of the PRDM16 gene were sequenced in 48 Uygur subjects with essential hypertension selected from 480 hypertensive patients and 819 normotensive controls. Representative variations were genotyped with TaqMan-PCR method. Association of variations of PRDM16 gene with hypertension was analyzed.</p><p><b>RESULTS</b>For the 4 genotyped representative variations (rs2236518, rs2282198, rs2493292 and rs870171), no significant difference in genotype distribution and allele frequencies has been found between the patient and control groups (P>0.05). By ANOVA analysis, none of the polymorphisms was significantly associated with systolic or diastolic blood pressure (P>0.05). Nor was significant difference in haplotypic frequencies between the two groups detected (P>0.05).</p><p><b>CONCLUSION</b>We have found no association between the four polymorphisms (rs2236518, rs2282198, rs2493292 and rs870171) of the PRDM16 gene with essential hypertension in ethnic Uygur population from Xinjiang.</p>

Research advances in suppressor of cytokine signaling 3 / 中国医学科学院学报

Suppressor of cytokine signaling(SOCS) 3, a novel type of cytokine signal transduction inhibitory molecules in family of SOCS, is mainly involved in Janus protein tyrosine kinase/signal transducer andantivator of transcription signaling pathway negative feedback regulation. It is involved in inflammation, oxidative stress, cell damage, and apoptosis. Meanwhile, it is closely related to atherosclerosis, obesity, glucose metabolism, insulin resistance, leptin, cancer, asthma, and rheumatic diseases. Therefore, SOCS-3 may become a therapeutic target of these diseases.

Epidemiological survey of lipid levels and factors in Kazakan people over 30-year old in Fukang of Xinjiang / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the lipids level in Kazakan individuals over 30-year-old in Fukang area of Xinjiang.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Genetic variations of bone morphogenetic protein 7 gene are associated with hypertriglyceridemia of Uygur Chinese in Xinjiang / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the association between the genetic variations of functional region in bone morphogenetic protein (BMP7) gene and dyslipidemia in Chinese Uygur individuals.</p><p><b>METHODS</b>The case-control study was conducted in 1514 Uygur Chinese based on epidemiological investigation. The all exons, segmental introns and the promoter regions of BMP7 gene were sequenced in 48 out of 1514 Uygur Chinese. Representative variations were then selected according to the minor allele frequency (MAF) and linkage disequilibrium, and genotyped using the TaqMan polymerase chain reaction method in 1514 Uygur Chinese, a relatively isolated general population in a relatively homogeneous environment, to observe the association between genetic variations of BMP7 gene and dyslipidemia.</p><p><b>RESULTS</b>Five novel and eight known variations in the BMP7 gene were identified. All genotype distributions were tested for deviations from Hardy-Weinberg equilibrium. There were significant differences of genotype distribution of rs6025422 between hypertriglyceridemia group and control group (P = 0.001). The levels of triglyceride (TG) showed a decreasing tendency in individuals with AA, AG and GG genotypes of rs6025422. Odd ratio (OR) value adjusted for age, gender, body mass index, smoking and alcohol drinking habits was 0.562 by logistic regression analysis (95%CI: 0.393 - 0.802, P = 0.002).</p><p><b>CONCLUSION</b>The present study shows rs6025422 polymorphism in the BMP7 gene is linked with hypertriglyceridemia phenotype in Uygur Chinese population.</p>

Negative association of STAMP2 gene polymorphisms with essential hypertension in Xinjiang Uygur population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the genetic polymorphisms of the six transmembrane protein of prostate 2 gene (STAMP2) and essential hypertension in Xinjiang Uygur population.</p><p><b>METHODS</b>The sequences of STAMP2 gene functional region were sequenced in Xinjiang Uygur population with hypertension. The representative variations selected were genotyped by TaqMan-PCR method in 2047 Uygur individuals, including 810 patients with hypertension and 1237 healthy subjects. The association of the genetic variations of the STAMP2 gene with hypertension in Uygur was analyzed.</p><p><b>RESULTS</b>In the three representative variations (rs8122, rs1981529 and rs34741656) genotyped, there were no significant differences in genotype distribution and allele frequencies between the essential hypertension and control groups (P > 0.05). In ANCOVA analysis, none of the polymorphisms was significantly associated with systolic blood pressure and diastolic blood pressure (P > 0.05). There were no significant differences in haplotype frequencies between the two groups either(P > 0.05).</p><p><b>CONCLUSION</b>There was no association of the three polymorphisms (rs8122, rs1981529 and rs34741656) in the STAMP2 gene with essential hypertension in Xinjiang Uygur population.</p>

Association of STEAP4 genetic polymorphisms with insulin resistance in Uygur Chinese general population / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the relationship between six-transmembrane epithelial antigen of prostate 4 (STEAP4) genetic polymorphisms and insulin resistance (IR) in Uygur Chinese general population.</p><p><b>METHODS</b>In this cross-sectional study on the metabolic diseases (e.g. obesity) among Uygur Chinese in Hetian, Xinjiang, China,from January to February 2007, 2127 Uygur individuals were enrolled. The sample size for IR subjects [homeostasis model assessment for insulin resistance (HOMA-IR) ≥2.3 65%] was 669, whereas that for non-IR controls was 664 (HOMA-IR≤1.335%). STEAP4 gene was sequenced in 50 Uygur Chinese individuals with IR (HOMA-IR≥2.3). The representative variations were selected from the population based on a r(2) cutoff of 0.8 and a minor allele frequency of >5% for case-control study.</p><p><b>RESULTS</b>Totally 16 variations including 10 novel variations (no reported in dbSNP) were identified in 50 Uygur individuals with IR. 7414 G/A (rs8122)(P/Pc=0.004/0.012)and 224A/G (rs1981529, Gly75Asp)(P/Pc=0.015/0.045)variations were significantly correlated with IR phenotype in Uygur subjects. As shown by multiple linear regression analysis, the mean values of waist circumference (WC) (P/Pc=0.032/0.256), body mass index (BMI) (P/Pc=0.004/0.032), HOMA-IR (P/Pc=0.010/0.08), and fasting insulin (P/Pc=0.023/0.184) among A (protection) allele carriers of rs8122 and the mean values of WC (P/Pc=0.005/0.040) and BMI (P/Pc=0.002/0.016) among G (protection) allele carriers of rs1981529 gradually declined. Haplotype 1 (rs8122 G- rs1981529 A- rs34741656 G) was significantly associated with a higher prevalence of IR (Permutation P=0.021).</p><p><b>CONCLUSION</b>STEAP4 genetic variations are likely to be associated with obesity-related insulin resistance in Uygur Chinese general population.</p>

A common variation within the STEAP4 gene exons is associated with obesity in Uygur general population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Coordinated regulation of nutrient and inflammatory responses by six transmembrane epithelial antigen of prostate 4 (STEAP4) was essential for metabolic homeostasis. STEAP4 expression in human white adipose tissue was associated with obesity. This study aimed to evaluate association between STEAP4 genetic polymorphisms and obesity in Uygur Chinese general population.</p><p><b>METHODS</b>The functional regions of STEAP4 gene were sequenced in 96 Uygur with obesity (body mass index (BMI) > 30 kg/m²). Representative variations were selected according to the function and linkage disequilibrium and genotyped in 1507 obesity (BMI ≥ 25 kg/m²) and 825 non-obesity control (BMI < 25 kg/m²), all of whom were selected from epidemiology study of obesity-related diseases during January to February 2007 among Uygur population in Hetian area of Xinjiang Uygur Autonomous Region.</p><p><b>RESULTS</b>Fourteen novel and 6 known single nucleotide polymorphism (SNPs), including 2 nonsynonymous SNPs (nsSNPs), in the STEAP4 gene were identified. Of the 3 representative SNPs, the nsSNP rs1981529 (Gly75Asp, 224A/G) was significantly associated with obesity phenotype (additive P/Pc = 0.001/0.006, dominant P/Pc = 0.003/0.018, odds ratio (OR) and 95% confidence interval (CI) adjusted for age, gender and drinking 0.755 (0.641 - 0.890) and 0.750 (0.621 - 0.907), respectively). By the multiple linear regression analysis, the quantitative phenotypes of BMI (P/Pc = 0.002/0.004) and waist circumference (P/Pc = 0.004/0.008) were found to be significantly associated with the genotypes of rs1981529 (Gly75Asp, 224A/G) in Uygur general population, and effect size (beta value) of one allele G of rs1981529 (Gly75Asp, 224A/G) was - 0.553 kg/m² for BMI and - 1.311 cm for waist circumference after controlling age, gender and drinking factors.</p><p><b>CONCLUSIONS</b>The present study shows an association of the common variation rs1981529 (Gly75Asp, 224A/G) in the STEAP4 gene with obesity in Uygur general population. Further studies should replicate the results using larger populations.</p>

Association of the genetic variations of bone morphogenetic protein 7 gene with diabetes and insulin resistance in Xinjiang Uygur population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between the genetic variations of the functional region in bone morphogenetic protein gene (BMP7) with type 2 diabetes mellitus in Chinese Uygur individuals.</p><p><b>METHODS</b>A case-control study was conducted based on epidemiological investigation. A total of 717 Uygur subjects (276 males and 441 females) were selected and divided into two groups: diabetes mellitus group (n = 502, 191 males and 311 females) and control group (n = 215, 85 males and 130 females). All exons, flanking introns and the promoter regions of (BMP7) gene were sequenced in 48 Uygur diabetics. Representative variations were selected according to the minor allele frequency (MAF) and linkage disequilibrium and genotyped using the TaqMan polymerase chain reaction method in 717 Uygur individuals, a relatively isolated general population in a relatively homogeneous environment and a case-control study was conducted to test the association between the genetic variations of (BMP7) gene and type 2 diabetes mellitus.</p><p><b>RESULTS</b>Five novel and 8 known variations in the (BMP7) gene were identified. All genotype distributions were tested for deviations from Hardy-Weinberg equilibrium (P> 0.05). There was significant difference of genotype distribution of rs6025422 between type 2 diabetes mellitus and control groups in the male population (P< 0.05, P adjusted > 0.05), but there was no difference in total and female population (P> 0.05). And the means of fasting blood glucose (FBG), fasting insulin and HOMA-index significantly decreased in individuals with AA, AG and GG genotypes of rs6025422 in male population (P< 0.05), but not in total and female population (P> 0.05). The logistic regression analysis showed that GG genotype of rs6025422 variation might be a protective factor for diabetes in male (OR= 0.637, 95% confidence interval 0.439-0.923, P< 0.05).</p><p><b>CONCLUSION</b>The present study suggests that the rs6025422 polymorphism in (BMP7) gene may be associated with diabetes mellitus and insulin resistance in Uygur men.</p>

Relationship between rs3865418 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene and obesity in Kazakh general population / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationships between rs3865418 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene and obesity in Kazakh general population.</p><p><b>METHODS</b>Based on a cross-sectional epidemiological study in a Kazakh general population, a case-control study was conducted. The rs3865418 polymorphism in a Kazakh general population (856 subjects, including 364 males and 492 females; 478 in obesity group and 378 in normal control group) was genotyped by TaqMan polymerase chain reaction, and the relationship between rs3865418 polymorphism and obesity was analyzed.</p><p><b>RESULTS</b>The rs3865418 polymorphism was successfully genotyped in 851 Kazakh subjects. The distribution of the genotypes and alleles of rs3865418 polymorphism did not differ significantly between the obesity group and normal control group in terms of general populations, males, and females (all P > 0.05). The waist circumference showed a tendency of C/C > C/T > T/T in males and C/C < C/T < T/T in females, but without statistical significance (P > 0.05).</p><p><b>CONCLUSIONS</b>The rs3865418 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene may not be associated with obesity in Kazakh general population. In other words, it is not a predisposing factor for obesity in Kazakh.</p>

Association between rs4149601 polymorphism and essential hypertension in Kazakh / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between a functional rs4149601 polymorphism of neural precursor cell expressed developmentally downregulated 4-like gene (NEDD4L) and essential hypertension in Kazakh.</p><p><b>METHODS</b>In this population-based association study, the genotypes of rs4149601 polymorphism were identified by TaqMan PCR in 883 subjects (male 375 383 hypertensives) and its distribution and relationship to hypertension were studied. The association between haplotype (rs4149601, 296921-296923delTTG, rs2288774 and rs2288775, the last three polymorphisms are representative variations identified from 94 Kazakh hypertensive individuals by screening the functional region of NEDD4L previously) and hypertension was also investigated.</p><p><b>RESULTS</b>The genotype distribution of rs4149601 polymorphism was in Hardy-Weinberg equilibrium. The genotype distribution of rs4149601 polymorphism was similar between the essential hypertension patients and the control individuals (all P > 0.05). In the haplotype-based case-control analysis, the distribution of the haplotypes was not significantly different between the case and the control individuals in total and in male subjects but the frequency of D-C-G-G (296921-3delTTG/rs2288774/rs2288775/rs4149601) haplotype was significantly higher in hypertensive than in control individuals in female (P = 0.026).</p><p><b>CONCLUSION</b>Our results suggested that D-C-G-G haplotype of NEDD4L but not rs4149601 polymorphism was linked with hypertension in Kazakh.</p>

Serum neuropeptide Y level in hypertensive patients with obstructive sleep apnea syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the potential role of neuropeptide Y (NPY) in the pathophysiological process of hypertension caused by obstructive sleep apnea syndrome (OSAS).</p><p><b>METHODS</b>The concentration of serum NPY were measured with radioimmunoassay (RIA) in 417 subjects (97 normotensive controls without OSAS, 113 cases of normotensive with OSAS, 73 cases of hypertensive without OSAS and 134 cases of hypertensive with OSAS. Further, the mean NPY level were compared in four groups and the possible effective factors on NPY were discussed.</p><p><b>RESULTS</b>(1) The concentration of NPY in four groups were (50.5 +/- 37.2) pmol/L in normal controls, (76.0 +/- 39.9) pmol/L in normotensive with OSAS group, (66.9 +/- 36.2) pmol/L in hypertensive without OSAS group and (86.8 +/- 36.8) pmol/L in hypertensive with OSAS group. Whether the patients with OSAS combined with hypertension or not, the concentration of NPY in the serum raised remarkably compared with those without OSAS and hypertension, the highest level of serum NPY was detected in OSAS combined with hypertension group. (2) Pearson correlation analysis indicated that both SBP and DBP related to the serum NPY significantly in non-OSAS group (AHI <10), while the BMI, abdominal circumference, AHI as well as the lowest level of SaO2 correlated to NPY besides SBP in OSAS group with (AHI > or =10). (3) Multiple linear regression model showed that the abdominal circumference and AHI were contributing factors to SBP, while neck circumference and BMI were contributing factors to DBP. The level of NPY in the serum were significantly affected by AHI and BMI, in which the former one had greater influence.</p><p><b>CONCLUSION</b>The increased level of serum NPY may play weakly potential roles in the pathophysiological process of hypertension caused by OSAS.</p>

Association of the rs4149601 polymorphism of NEDD4L gene with obesity in Xinjiang Kazakh population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the rs4149601 polymorphisms of neural precursor cell expressed developmentally downregulated 4-like gene (NEDD4L) and obesity in Xinjiang Kazakh population.</p><p><b>METHODS</b>The rs4149601 polymorphism of the NEDD4L gene was genotyped in a Xinjiang Kazakh general population including 856 subjects (aged 30 to 60 years, 478 obese and 378 control individuals).</p><p><b>RESULTS</b>The polymorphism was successfully genotyped in 853 Xinjiang Kazakh subjects. The distribution of the additive model and dominant model (AG+ AA vs. GG) of the rs4149601 polymorphism differed significantly between the case and control in both total and females (all P< 0.05). After adjusting for confounding factors, logistic regression analysis showed that the rs4149601 polymorphism (in dominant model) was significantly associated with obesity (OR= 1.479, 95% CI: 1.103-1.983, P= 0.009) in Kazakh. Covariate variance analysis showed that compared with subjects with AA + AG genotypes, the waist circumference was significantly higher in subjects with GG genotype after adjusting for age, smoking and drinking (P= 0.028).</p><p><b>CONCLUSION</b>The genetic variations of the NEDD4L gene may be associated with obesity in Xinjiang Kazakh general population.</p>