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>

Genetic polymorphism of six transmembrane protein of prostate 2 associated with diabetes mellitus in Xinjiang Uygur population / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the association between the genetic variations of six transmembrane protein of prostate 2 (STAMP2) with type 2 diabetes mellitus (T2DM) in Xinjiang Uygur population.</p><p><b>METHODS</b>A case-control study was conducted based on epidemiological investigation. A total of 1838 Uygur subjects were selected and divided into two groups: T2DM group (n=274) and control group (n=1564). All exons, flanking introns, and the promoter regions of STAMP2 gene were sequenced in 48 Uygur Xinjiang population with diabetes. Representative variations selected were genotyped by TaqMan-PCR method in all individuals.</p><p><b>RESULTS</b>Ten novel and 6 known variations in the STAMP2 gene were identified. The distribution of genotype rs8122 significantly differed between T2DM group and control group (P=0.05), whereas the distribution of genotypes rs1981529 and rs34741656 showed no such difference. The fasting insulin in the total cohort and homeostasis model of assessment index in females showed significant difference between these two groups (P<0.05), while the adjusted P value showed no statistical significance (P>0.05). In the male population, the different genotypes of rs8122 variation of STAMP2 gene were not significantly different (P>0.05).</p><p><b>CONCLUSION</b>Three polymorphisms (rs8122, rs1981529 and rs34741656) of STAMP2 gene may be not related with T2DM in Xinjiang Uygur population.</p>

Association between genetic polymorphism of the six-transmembrane protein of prostate 2 and obesity in Uygur / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between genetic variations of the six transmembrane protein of prostate 2 (STAMP2) and obesity in Xinjiang Uygur population.</p><p><b>METHODS</b>A total of 2332 Uygur subjects (1455 obesity and 877 non-obesity control subjects) were included in this case-control study based on epidemiological survey. Genetic variations of STAMP2 gene functional region were sequenced. The representative variations selected were genotyped by TaqMan-PCR method.</p><p><b>RESULTS</b>Twenty genetic variations, including 14 novel variations, were identified. The genotype distributions of the control group and obesity group were in the Hardy-Weinberg equilibrium (both P > 0.05). The frequency of AA of rs1981529 (67.6% vs. 62.8%, P < 0.05) and the frequency of G-A-G haplotype (62.4% vs. 58.9%, P < 0.05) in obesity group were significantly higher than that in controls while the frequency of A-G-G haplotype was significantly lower in the obesity patients than that in the control group (17% vs. 20%, P < 0.05). After adjusting age, sex, smoking and drinking, logistic regression analysis showed that the AA genotype of rs1981529 (OR: 1.276, 95%CI: 1.049 - 1.552; P < 0.05) and the G-A-G haplotype (OR: 1.356, 95%CI: 1.007 - 1.862, P < 0.05) were the independent risk factors for obesity in this cohort.</p><p><b>CONCLUSION</b>The AA genotype of rs1981529 and G-A-G haplotype are associated with obesity in Uygur population of Xinjiang.</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>

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>

Genetic variation and association of STEAP4 gene with metabolic syndrome in Chinese Uygur patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the genetic variations of the six transmembrane epithelial antigen of prostate 4 gene (STEAP4) in Chinese Uygur patients with metabolic syndrome (MetS) and to analyze the association of the representative genetic variations of STEAP4 gene with MetS in the population.</p><p><b>METHODS</b>The sequences of STEAP4 gene functional region (all exons, exon-intron boundaries and the putative promoter region, including the -1 kb 5'and 3'untranslated regions) were amplified and sequenced for patients with MetS. The representative variations were selected based on the function (missense mutation) and linkage disequilibrxium (γ² > 0.8) and genotyped with TaqMan-PCR method in 1910 general populations (682 MetS and 1228 non-MetS controls). The subjects were selected from the cross-sectional study of obesity, hypertension, diabetes, dyslipidemia from January to February 2007 among Uygur people, a relatively isolated population with a relatively homogeneous environment, in Hextian area in Xinjiang Uygur Autonomous Region.</p><p><b>RESULTS</b>(1) Fourteen novel and six known single nucleotide polymorphisms (SNPs) or mutations, including 2 missense mutations, were identified at the functional region of STEAP4 gene in 96 Uygur patients with MetS. The minor allele frequencies of the SNPs of STEAP4 gene in Uygur population were different from that in European and Chinese Han in Beijing area. (2) The SNP 364G/A (rs34741656, Ala122Thr) was significantly associated with MetS [dominant model P = 0.034, OR = 0.757(95%CI: 0.584-0.982) adjusted for age and gender], and was associated with fasting blood glucose (FBG) (P = 0.049) and 2-hour postprandial glucose (2HPG) (P = 0.027) levels in controls. In this SNP, the AA carriers had lower blood glucose levels compared with subjects carrying GG and GT genotypes. (3) The common haplotype H4 (rs8122/rs1981529/ rs34741656, G-A-A), may be associated with MetS (permutation P = 0.089).</p><p><b>CONCLUSION</b>STEAP 4 genetic polymorphisms may be associated with MetS risk in Chinese 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>

Analysis on vascular risk factors accompanied with high-normal blood pressure among Uygur,Kazak,Mongolian and Han populations in Boertala region of Xinjiang, China / 中华流行病学杂志

Objective To study the prevalence and distribution of high-normal blood pressure (BP) and the prevalence rates of risk factors related to cardiovascular diseases (CVD) among Uygur,Kazak,Mongolian and Han populations in Boertala Mongol Autonomous Prefecture of Xinjiang. Methods 4325 Subjects,with numbers of Uygur,Kazak,Mongolian,Han ethnicities as 1247,1047,817,1214 cases,respectively and aged 20-79 years,were selected from the cross-sectional study on hypertension in Boertala Mongol Autonomous Prefecture of Xinjiang. The prevalence rates of related risk factors on CVD were analyzed among multiethnic populations with high-normal BP. Results (1) The prevalence rates of high-normal BP were 39.2%,34.5%,36.0%,36.5% respectively in Uygur,Kazak,Mongolian,Han populations. The prevalence rate of aged <40 years in Uygur,Kazak,Mongolian was higher than that of aged 40-60 (P=0.000,0.006,0.016 respectively in Uygur,Kazak,Mongolian) and >60 years (all the P=0.000 in the three ethnic populations) in the same ethnic population. (2) In the high-normal BP groups,subjects with both SBP (120-139 mm Hg) and DBP (80-89 mm Hg) at high-normal BP level accounted for the majority (>45%) while subjects with only DBP (80-89 mm Hg) at high-normal BP level had the lowest prevalence rate (>13%). (3) The prevalence rates of overweight-obesity (body mass index≥24.0 kg/m~2),visceral obesity (waist circumference≥male 85 cm/female 80 cm),dyslipidemia and≥1 risk factors of CVD in multiethnic populations respectively were≥57%,62%,43 % and 82 %. (4) Analyzed by multiple regression,aging,over-weight and or obesity,being male etc. were risk factors for high-normal BP. Conclusion High-normal blood pressure was common among aged 20-79 years Uygur,Kazak,Mongolian,Han populations,especially among people <40 years,in Xinjiang Boertala region,which was often accompanied by others risk factors of cardiovascular disease. Prevention and control programs on risk factors for population with high-normal blood pressure need to be strongly advocated.

Distribution of genetic variation of neural precursor cell expressed developmentally down-regulated 4 gene in Kazak Chinese and its association with hypertension / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyze the association between the genetic variations of functional region in neural precursor cell expressed developmentally down-regulated 4 ( NEDD4) gene and hypertension in Kazak Chinese in Xinjiang Uygur Autonomous Region.</p><p><b>METHODS</b>The sequences of NEDD4 gene functional region (all exons, exon-intron boundaries, and the putative promoter region, including the 5'- and 3'-untranslated regions 1 kb) were sequenced in Kazak Chinese patients with hypertension. The representative variations selected were genotyped by TaqMan-PCR method in 938 Kazak individuals, including 451 hypertensive patients and 487 normotensive subjects. The association between genetic variations of NEDD4 and hypertension in Kazak was analyzed.</p><p><b>RESULTS</b>Thirteen novel and 15 known single nucleotide polymorphism (SNPs) or mutations, including 7 missense mutations, were identified at the function region of NEDD4 gene in 94 Kazak patients with hypertension. In the nine representative variations genotyped, 4 rare missense mutations [77291T>G (S189R), 77748 C>T (R342W), 123925C>T (P152L), rs1912403 (76821A>G, M33V)] were not specific for the prevalence of hypertension; in addition, the distribution of 5 common SNPs [77943A>C (N407H), rs2303580 (132882G>A, R607Q), rs8028559 (154845T>C), rs7162435 (164420A>G), and rs11550869 (165622C>G)] and haplotypes were not significantly different between the hypertensive patients and normotensive subjects (P>0.05).</p><p><b>CONCLUSION</b>The NEDD4 gene polymorphisms is no associated with hypertension in Kazak Chinese population.</p>