Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short st...Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short stature （ISS） in the Chinese Han population. Methods A case- control study was carried out on a cohort of 198 ISS patients and 306 healthy controls. A total of 106 tagging single nucleotide polymorphisms （tagSNPs） from the six genes were selected from the HapMap （haplotype map of the human genome ） Han Chinese in the Beijing subset. Results of genotyping conducted by high- throughput lllumina GoldenGateTM Assay were analyzed by statistical software. Results Both individual tagSNPs and haplotypes showed an association with 1SS in the Han Chinese population （ P 〈 O. 05 ）. For each single test, both allele and genotype were tested. By allele frequency analysis, six positive SNP sites （ rsNo. 1, rsNo. 2, rsNo. 3, rsNo. 4, rsNo. 5, and rsNo. 6） of 3 genes （ JAK2, 1GF-1R, and GHR） were found having associations with ISS. By genotype frequency analysis, there were significant differences between the patient and control groups in the following SNP sites： 4 sites in JAK2 gene （ rsNo. 1, rsNo. 2, rsNo. 3, and rsNo. 4） and 1 site in GHR gene （ rsNo. 6）. The risk which affected ISS was found related to the JAK2 gene in 4 sites （ increase in rsNo. 1 and decrease in rsNo. 2, rsNo. 3, and rsNo. 4 ） and to the GHR gene in 1 site （decrease in rsNo. 6）. They were four haplotypes in gene of IGF-1R as ＂TGC＂, ＂CGCT＂, ＂TA＂, and ＂ CA＂, one haplotype in IGFBP-3 as ＂TA＂, and one haplotype in JAK2 as ＂CTG＂, which revealed high significance for risks of affecting ISS. At last, multivariate logistic regression analysis of specific site rsNo. 6 of the GHR gene revealed that the serum IGF-1 was related to genotypes AA and AC, with genotype CC as the reference （ P =0. 015）. Conclusion Genetic variances in six genes within the GH/IGF-1 axis may be important etiological factors for ISS in the Chinese Han population.展开更多
目的:分析不同体重指数(body mass index,BMI)的特发性矮小症(idiopathic short stature,ISS)患儿在重组人生长激素(recombinant human growth hormone,rhGH)治疗下的疗效差异及安全性。方法:选取于河北北方学院附属第一医院接受rhGH治...目的:分析不同体重指数(body mass index,BMI)的特发性矮小症(idiopathic short stature,ISS)患儿在重组人生长激素(recombinant human growth hormone,rhGH)治疗下的疗效差异及安全性。方法:选取于河北北方学院附属第一医院接受rhGH治疗的ISS患儿为研究对象,根据7岁以下儿童生长标准及中国6~18岁学龄儿童青少年性别、年龄、体质指数、超重与肥胖界值,将ISS患儿分为BMI正常组、超重组、肥胖组,测定三组患儿治疗前、治疗3个月及6个月后的身高(height,Ht)、BMI、生长速率(growth velocity,GV)、身高标准差积分(height standard deviation score,HtSDS)、胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)、胰岛素样生长因子结合蛋白-3(insulin like growth factor binding-protein-3,IGFBP-3)、空腹血糖(fasting blood glucose,FBG)、甲状腺功能及肝功能。结果:三组ISS患儿在rhGH治疗后Ht、GV、HtSDS、IGF-1、IGFBP-3均较治疗前增加(P<0.05)。BMI正常组患儿Ht、GV和HtSDS增长量明显高于超重组及肥胖组(P<0.05),超重组与肥胖组相比无明显差异(P>0.05)。BMI正常组患儿在治疗6个月后BMI较治疗前增加(P<0.05),而超重组及肥胖组BMI均较前下降(P<0.05)。rhGH治疗对FBG、甲状腺功能、肝功能无明显影响。结论:rhGH能明显提高ISS患儿的Ht、HtSDS、GV、IGF-1、IGFBP-3水平,BMI正常的ISS患儿的疗效明显好于超重组及肥胖组,超重及肥胖ISS患儿疗效无明显差异,rhGH治疗具有较好的安全性。展开更多
基金Supported by National Natural Science Foundation of China(30771029)
文摘Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short stature （ISS） in the Chinese Han population. Methods A case- control study was carried out on a cohort of 198 ISS patients and 306 healthy controls. A total of 106 tagging single nucleotide polymorphisms （tagSNPs） from the six genes were selected from the HapMap （haplotype map of the human genome ） Han Chinese in the Beijing subset. Results of genotyping conducted by high- throughput lllumina GoldenGateTM Assay were analyzed by statistical software. Results Both individual tagSNPs and haplotypes showed an association with 1SS in the Han Chinese population （ P 〈 O. 05 ）. For each single test, both allele and genotype were tested. By allele frequency analysis, six positive SNP sites （ rsNo. 1, rsNo. 2, rsNo. 3, rsNo. 4, rsNo. 5, and rsNo. 6） of 3 genes （ JAK2, 1GF-1R, and GHR） were found having associations with ISS. By genotype frequency analysis, there were significant differences between the patient and control groups in the following SNP sites： 4 sites in JAK2 gene （ rsNo. 1, rsNo. 2, rsNo. 3, and rsNo. 4） and 1 site in GHR gene （ rsNo. 6）. The risk which affected ISS was found related to the JAK2 gene in 4 sites （ increase in rsNo. 1 and decrease in rsNo. 2, rsNo. 3, and rsNo. 4 ） and to the GHR gene in 1 site （decrease in rsNo. 6）. They were four haplotypes in gene of IGF-1R as ＂TGC＂, ＂CGCT＂, ＂TA＂, and ＂ CA＂, one haplotype in IGFBP-3 as ＂TA＂, and one haplotype in JAK2 as ＂CTG＂, which revealed high significance for risks of affecting ISS. At last, multivariate logistic regression analysis of specific site rsNo. 6 of the GHR gene revealed that the serum IGF-1 was related to genotypes AA and AC, with genotype CC as the reference （ P =0. 015）. Conclusion Genetic variances in six genes within the GH/IGF-1 axis may be important etiological factors for ISS in the Chinese Han population.
文摘目的:分析不同体重指数(body mass index,BMI)的特发性矮小症(idiopathic short stature,ISS)患儿在重组人生长激素(recombinant human growth hormone,rhGH)治疗下的疗效差异及安全性。方法:选取于河北北方学院附属第一医院接受rhGH治疗的ISS患儿为研究对象,根据7岁以下儿童生长标准及中国6~18岁学龄儿童青少年性别、年龄、体质指数、超重与肥胖界值,将ISS患儿分为BMI正常组、超重组、肥胖组,测定三组患儿治疗前、治疗3个月及6个月后的身高(height,Ht)、BMI、生长速率(growth velocity,GV)、身高标准差积分(height standard deviation score,HtSDS)、胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)、胰岛素样生长因子结合蛋白-3(insulin like growth factor binding-protein-3,IGFBP-3)、空腹血糖(fasting blood glucose,FBG)、甲状腺功能及肝功能。结果:三组ISS患儿在rhGH治疗后Ht、GV、HtSDS、IGF-1、IGFBP-3均较治疗前增加(P<0.05)。BMI正常组患儿Ht、GV和HtSDS增长量明显高于超重组及肥胖组(P<0.05),超重组与肥胖组相比无明显差异(P>0.05)。BMI正常组患儿在治疗6个月后BMI较治疗前增加(P<0.05),而超重组及肥胖组BMI均较前下降(P<0.05)。rhGH治疗对FBG、甲状腺功能、肝功能无明显影响。结论:rhGH能明显提高ISS患儿的Ht、HtSDS、GV、IGF-1、IGFBP-3水平,BMI正常的ISS患儿的疗效明显好于超重组及肥胖组,超重及肥胖ISS患儿疗效无明显差异,rhGH治疗具有较好的安全性。
