BACKGROUND Adiponectin(ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual's predisposition to...BACKGROUND Adiponectin(ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual's predisposition to metabolic syndrome and type 2 diabetes. Moreover, women with gestational diabetes mellitus(GDM) are at an increased risk of developing type 2 diabetes. Several studies have been conducted previously to assess the association between ADIPOQ polymorphisms and GDM; however, the results of the association are inconclusive.AIM To quantitatively evaluate the association between ADIPOQ +45 T/G, +276 G/T,and-11377 C/G polymorphisms and the risk of GDM.METHODS A systematic search of EMBASE, PubMed, CNKI, Web of Science, and WANFANG DATA was conducted up to October 20, 2018. We calculated merged odds ratios(ORs) with 95% confidence intervals(CIs) using a fixed-effects or random-effects model depending on the between-study heterogeneity to evaluate the association between AIDPOQ +45 T/G, +276 G/T, and-11377 C/G polymorphisms and the risk of GDM. Subgroup analysis was performed by ethnicity. Publication and sensitivity bias analyses were performed to test the robustness of the association. All statistical analyses were conducted using Stata 12.0.RESULTS Nine studies of +45 T/G included 1024 GDM cases and 1059 controls, five studies of +276 G/T included 590 GDM cases and 595 controls, and five studies of-11377 C/G included 722 GDM cases and 791 controls. Pooled ORs indicated that+45 T/G increased GDM risk in Asians(allelic model: OR = 1.47, 95%CI: 1.27-1.70,P = 0.000; dominant model: OR = 1.54, 95%CI: 1.27-1.85, P = 0.000; recessive model: OR=2.00, 95%CI: 1.43-2.85, P = 0.000), not in South Americans(allelic model: OR = 1.21, 95%CI: 0.68-2.41, P = 0.510; dominant model: OR = 1.13, 95%CI:,0.59-2.15, P = 0.710; recessive model: OR = 2.18, 95%CI: 0.43-11.07, P = 0.350).There were no significant associations between +276 G/T(allelic model: OR = 0.88,95%CI: 0.74-1.05, P = 0.158; dominant model: OR = 0.91, 95%CI: 0.65-1.26, P =0.561; recessive model: OR = 0.82, 95%CI: 0.64-1.05, P = 0.118) or-11377 C/G(allelic model: OR = 0.96, 95%CI: 0.72-1.26, P = 0.750; dominant model: OR = 1.00,95%CI: 0.73-1.37, P = 0.980; recessive model: OR = 0.90, 95%CI: 0.61-1.32, P =0.570) and the risk of GDM.CONCLUSION Our meta-analysis shows the critical role of the ADIPOQ +45 T/G polymorphism in GDM, especially in Asians. Studies focused on delineating ethnicity-specific factors with larger sample sizes are needed.展开更多
Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardio- myocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene poly...Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardio- myocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene polymorphism on myocardial fibrosis. Our study investigates the influence of the SNP ＋45 polymorphism of the adi- ponectin gene and serum levels of adiponectin on myocardial fibrosis in patients with essential hypertension. A case-control study was conducted on 165 hypertensive patients and 126 normotensive healthy controls. The geno- types of adiponectin gene polymorphisms were detected by the polymerase chain reaction （PCR） method. Serum concentrations of procollagen were measured by a double antibody sandwich enzyme-linked immunosorbent assay （ELISA） in all subjects. The integrated backscatter score （IBS） was measured in the left ventricular myocardium using echocardiography. The serum levels of adiponectin in hypertensive patients were significantly lower than those in the normal control group （（2.69±1.0） μg/ml vs. （4.21±2.89） μg/ml, respectively, P〈0.001）. The serum levels of type-Ⅰ procoilagen carboxyl end peptide （PiCP） and type-Ⅲprocollagen ammonia cardinal extremity peptide （PIIINP） in the hypertension group were significantly higher than those in the control group. In the hypertension group, serum levels of adiponectin were significantly and negatively related to the average acoustic intensity and corrected acoustic intensity of the myocardium （t=0.46 and 0.61, respectively, P〈0.05 for both）. The serum levels of PICP and PIIINP were sig- nificantly different among the three genotypes of SNP ＋45 （P〈0.01）. Logistic regression analyses showed that sex and genotype （GG＋GT） were the major risk factors of myocardial fibrosis in hypertensive patients （OR=5.343 and 3.278, respectively, P〈0.05）. These data suggest that lower levels of adiponectin and SNP ＋45 polymorphism of the adi- ponectin gene are likely to play an important role in myocardial fibrosis in hypertensive patients.展开更多
Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in th...Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in the APMI gene associated with T2DM in Han nationality. Methods The APMI gene 5＇-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance （IGT） and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically asses,sed. Results Three SNPs were identified in the APMI gene 5＇-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls （G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03）. Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-LI cell line. Conclusion SNP - 11377 G/C in the proximal promoter region of the APM 1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.展开更多
This study was aimed to explore the associations between the combined effects of several polymorphisms in the PPAR-γ and RXR-α gene and environmental factors with the risk of metabolic syndrome by back-error propaga...This study was aimed to explore the associations between the combined effects of several polymorphisms in the PPAR-γ and RXR-α gene and environmental factors with the risk of metabolic syndrome by back-error propaga- tion artificial neural network （BPANN）. We established the model based on data gathered from metabolic syndrome patients （n = 1012） and normal controls （n = 1069） by BPANN. Mean impact value （MIV） for each input variable was calculated and the sequence of factors was sorted according to their absolute MIVs. Generalized multifactor dimensionality reduction （GMDR） confirmed a joint effect of PPAR-9＂ and RXR-a based on the results from BPANN. By BPANN analysis, the sequences according to the importance of metabolic syndrome risk fac- tors were in the order of body mass index （BMI）, serum adiponectin, rs4240711, gender, rs4842194, family history of type 2 diabetes, rs2920502, physical activity, alcohol drinking, rs3856806, family history of hypertension, rs1045570, rs6537944, age, rs17817276, family history of hyperlipidemia, smoking, rs1801282 and rs3132291. However, no polymorphism was statistically significant in multiple logistic regression analysis. After controlling for environmental factors, A1, A2, B1 and B2 （rs4240711, rs4842194, rs2920502 and rs3856806） models were the best models （cross-validation consistency 10/10, P = 0.0107） with the GMDR method. In conclusion, the interaction of the PPAR-γ and RXR-α gene could play a role in susceptibility to metabolic syndrome. A more realistic model is obtained by using BPANN to screen out determinants of diseases of multiple etiologies like metabolic syndrome.展开更多
We observed the polymorphism distribution and coaction of uncoupling protein 3（UCP3）-55C/T,adiponectin（APN）＋45T/G and tumor necrosis factor（TNF）-α-308G/A on the onset and development of T2DM in a Northern Chin...We observed the polymorphism distribution and coaction of uncoupling protein 3（UCP3）-55C/T,adiponectin（APN）＋45T/G and tumor necrosis factor（TNF）-α-308G/A on the onset and development of T2DM in a Northern Chinese Han population of 213[100 type 2 diabete（T2DM） patients and 113 health control subjects] by polymerase chain reaction-restriction fragment length polymorphisum（PCR-RFLP） method.Results demonstrate the polymorphism of UCP3-55C/T,APN＋45T/G,and TNF-α-308G/A related to T2DM onset and developement.And the individuals carrying UCP3-55T,APN＋45G and TNF-α-308A allele had higher T2DM risk.Those results are the first report to evaluate the association of the coaction of UCP3,APN,TNF-α genes polymorphism on T2DM risk and the susceptibility of T2DM in the Northern Chinese Han population.展开更多
基金Supported by the National Nature Science Foundation of China,No.81773535
文摘BACKGROUND Adiponectin(ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual's predisposition to metabolic syndrome and type 2 diabetes. Moreover, women with gestational diabetes mellitus(GDM) are at an increased risk of developing type 2 diabetes. Several studies have been conducted previously to assess the association between ADIPOQ polymorphisms and GDM; however, the results of the association are inconclusive.AIM To quantitatively evaluate the association between ADIPOQ +45 T/G, +276 G/T,and-11377 C/G polymorphisms and the risk of GDM.METHODS A systematic search of EMBASE, PubMed, CNKI, Web of Science, and WANFANG DATA was conducted up to October 20, 2018. We calculated merged odds ratios(ORs) with 95% confidence intervals(CIs) using a fixed-effects or random-effects model depending on the between-study heterogeneity to evaluate the association between AIDPOQ +45 T/G, +276 G/T, and-11377 C/G polymorphisms and the risk of GDM. Subgroup analysis was performed by ethnicity. Publication and sensitivity bias analyses were performed to test the robustness of the association. All statistical analyses were conducted using Stata 12.0.RESULTS Nine studies of +45 T/G included 1024 GDM cases and 1059 controls, five studies of +276 G/T included 590 GDM cases and 595 controls, and five studies of-11377 C/G included 722 GDM cases and 791 controls. Pooled ORs indicated that+45 T/G increased GDM risk in Asians(allelic model: OR = 1.47, 95%CI: 1.27-1.70,P = 0.000; dominant model: OR = 1.54, 95%CI: 1.27-1.85, P = 0.000; recessive model: OR=2.00, 95%CI: 1.43-2.85, P = 0.000), not in South Americans(allelic model: OR = 1.21, 95%CI: 0.68-2.41, P = 0.510; dominant model: OR = 1.13, 95%CI:,0.59-2.15, P = 0.710; recessive model: OR = 2.18, 95%CI: 0.43-11.07, P = 0.350).There were no significant associations between +276 G/T(allelic model: OR = 0.88,95%CI: 0.74-1.05, P = 0.158; dominant model: OR = 0.91, 95%CI: 0.65-1.26, P =0.561; recessive model: OR = 0.82, 95%CI: 0.64-1.05, P = 0.118) or-11377 C/G(allelic model: OR = 0.96, 95%CI: 0.72-1.26, P = 0.750; dominant model: OR = 1.00,95%CI: 0.73-1.37, P = 0.980; recessive model: OR = 0.90, 95%CI: 0.61-1.32, P =0.570) and the risk of GDM.CONCLUSION Our meta-analysis shows the critical role of the ADIPOQ +45 T/G polymorphism in GDM, especially in Asians. Studies focused on delineating ethnicity-specific factors with larger sample sizes are needed.
基金Project supported by the Natural Science Foundation of Shandong Province, China (No. ZR2012HL19)the Science and Technology Development Plan of Tai’an City, China (No. 20113096)
文摘Adiponectin plays an important role in the development of hypertension, atherosclerosis, and cardio- myocyte hypertrophy, but very little was known about the influence of serum adiponectin or the adiponectin gene polymorphism on myocardial fibrosis. Our study investigates the influence of the SNP ＋45 polymorphism of the adi- ponectin gene and serum levels of adiponectin on myocardial fibrosis in patients with essential hypertension. A case-control study was conducted on 165 hypertensive patients and 126 normotensive healthy controls. The geno- types of adiponectin gene polymorphisms were detected by the polymerase chain reaction （PCR） method. Serum concentrations of procollagen were measured by a double antibody sandwich enzyme-linked immunosorbent assay （ELISA） in all subjects. The integrated backscatter score （IBS） was measured in the left ventricular myocardium using echocardiography. The serum levels of adiponectin in hypertensive patients were significantly lower than those in the normal control group （（2.69±1.0） μg/ml vs. （4.21±2.89） μg/ml, respectively, P〈0.001）. The serum levels of type-Ⅰ procoilagen carboxyl end peptide （PiCP） and type-Ⅲprocollagen ammonia cardinal extremity peptide （PIIINP） in the hypertension group were significantly higher than those in the control group. In the hypertension group, serum levels of adiponectin were significantly and negatively related to the average acoustic intensity and corrected acoustic intensity of the myocardium （t=0.46 and 0.61, respectively, P〈0.05 for both）. The serum levels of PICP and PIIINP were sig- nificantly different among the three genotypes of SNP ＋45 （P〈0.01）. Logistic regression analyses showed that sex and genotype （GG＋GT） were the major risk factors of myocardial fibrosis in hypertensive patients （OR=5.343 and 3.278, respectively, P〈0.05）. These data suggest that lower levels of adiponectin and SNP ＋45 polymorphism of the adi- ponectin gene are likely to play an important role in myocardial fibrosis in hypertensive patients.
基金supported by the Capital Development Fund Project (Grant No. 2002-1017).
文摘Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in the APMI gene associated with T2DM in Han nationality. Methods The APMI gene 5＇-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance （IGT） and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically asses,sed. Results Three SNPs were identified in the APMI gene 5＇-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls （G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03）. Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-LI cell line. Conclusion SNP - 11377 G/C in the proximal promoter region of the APM 1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.
基金supported by the National Natural Science Foundation of China Grant No.30771858Jiangsu Provincial Natural Science Foundation Grant No.BK2007229Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘This study was aimed to explore the associations between the combined effects of several polymorphisms in the PPAR-γ and RXR-α gene and environmental factors with the risk of metabolic syndrome by back-error propaga- tion artificial neural network （BPANN）. We established the model based on data gathered from metabolic syndrome patients （n = 1012） and normal controls （n = 1069） by BPANN. Mean impact value （MIV） for each input variable was calculated and the sequence of factors was sorted according to their absolute MIVs. Generalized multifactor dimensionality reduction （GMDR） confirmed a joint effect of PPAR-9＂ and RXR-a based on the results from BPANN. By BPANN analysis, the sequences according to the importance of metabolic syndrome risk fac- tors were in the order of body mass index （BMI）, serum adiponectin, rs4240711, gender, rs4842194, family history of type 2 diabetes, rs2920502, physical activity, alcohol drinking, rs3856806, family history of hypertension, rs1045570, rs6537944, age, rs17817276, family history of hyperlipidemia, smoking, rs1801282 and rs3132291. However, no polymorphism was statistically significant in multiple logistic regression analysis. After controlling for environmental factors, A1, A2, B1 and B2 （rs4240711, rs4842194, rs2920502 and rs3856806） models were the best models （cross-validation consistency 10/10, P = 0.0107） with the GMDR method. In conclusion, the interaction of the PPAR-γ and RXR-α gene could play a role in susceptibility to metabolic syndrome. A more realistic model is obtained by using BPANN to screen out determinants of diseases of multiple etiologies like metabolic syndrome.
基金Supported by the Scientific Research Foundation of Jilin Province,China(Nos.2007-0722,2008-2123,20100942)the Grants from the Developing and Reforming Community of Jilin Provinces,China(Nos.2006-1550,20080925,2010-1928)
文摘We observed the polymorphism distribution and coaction of uncoupling protein 3（UCP3）-55C/T,adiponectin（APN）＋45T/G and tumor necrosis factor（TNF）-α-308G/A on the onset and development of T2DM in a Northern Chinese Han population of 213[100 type 2 diabete（T2DM） patients and 113 health control subjects] by polymerase chain reaction-restriction fragment length polymorphisum（PCR-RFLP） method.Results demonstrate the polymorphism of UCP3-55C/T,APN＋45T/G,and TNF-α-308G/A related to T2DM onset and developement.And the individuals carrying UCP3-55T,APN＋45G and TNF-α-308A allele had higher T2DM risk.Those results are the first report to evaluate the association of the coaction of UCP3,APN,TNF-α genes polymorphism on T2DM risk and the susceptibility of T2DM in the Northern Chinese Han population.
