中文摘要：

<正>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 casecontrol 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 highthroughput Illumina GoldenGate?Assay were analyzed by statistical software.Results Both individual tagSNPs and haplotypes showed an association with ISS in the Han Chinese population（P <0.05）.For each single test,both allele and genotype were tested.By allele frequency analysis,six positive SNP sites （rsNo.l,rsNo.2,rsNo.3,rsNo.4,rsNo.5,and rsNo.6）of 3 genes（JAK2,IGF-1 R,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-1 R 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.

英文摘要：

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