ASSOCIATION ANALYSIS OF POLYMORPHISMS IN SIX GENES WITHIN THE GH/IGF-1 AXIS IN PATIENTS WITH IDIOPATHIC SHORT STATURE IN THE CHINESE HAN POPULATION
- Author:
- No author available
- Journal Title:
- Medical Bulletin of Shanghai Jiaotong University
- Issue:
- 1
- DOI:
- 10.3969/j.issn.1674-8123.2012.01.001
- Key Word:
- association analysis;growth hormone (GH) /insulin-like growth;factor-1 (IGF1) axis;idiopathic short stature;polymorphism
Abstract： 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 GoldenGateTM Assay were analyzed by statistical software. Results Both individual tagSNPs and haplotypes showed an association with ISS in the Hun Chinese population ( P ＜ 0.05 ).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,IGF-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.
- [1]P, Cohen,A D, Rogol,C L, Deal,etc.Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop.[J].2008,93.
- [2]Ardlie KG,Butler JL,Lettre G,etc.Common genetic variation in eight genes of the GH/IGF1 axis does not contribute to adult height variation.[J].2007,122(2).
- [3]Karperien M,Walenkamp MJ,Denley A,etc.Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation.[J].2005,90(5).
- [4]K A, Woods,C, Camacho-Hübner,M O, Savage,etc.Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene.[J].1996,335(18).
- [5]Hofman Albert,Vaessen Norbert,Lamberts-StevenW J,etc.Association between genetic variation in the gene for insulin-like growth factor-I and low birthweight.[J].2002,359(9311).
- [6]Hiekkalinna T,Terwilliger JD.An utter refutation of the "Fundamental Theorem of the HapMap".[J].2006,14(4).
- [7]Wu X,Cooper RS,Boerwinkle E,etc.Combined analysis of genomewide scans for adult height: results from the NHLBI Family Blood Pressure Program.[J].2003,11(3).
- [8]Groop L,Sammalisto S,Suviolahti E,etc.A male-specific quantitative trait locus on 1p21 controlling human stature.[J].2005,42(12).
- [9]Hofman A,Pols HA,Witteman JC,etc.A polymorphism in the gene for IGF-I: functional properties and risk for type 2 diabetes and myocardial infarction.[J].2001,50(3).
- [10]Abuzzahab MJ,Chernausek SD,Kratzsch J,etc.IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation.[J].2003,349(23).
- [11]S, Amselem,P, Duquesnoy,O, Attree,etc.Laron dwarfism and mutations of the growth hormone-receptor gene.[J].1989,321(15).
- [12]Naomi E, Allen,Gwyneth K, Davey,Timothy J, Key,etc.Serum insulin-like growth factor I (IGF-I) concentration in men is not associated with the cytosine-adenosine repeat polymorphism of the IGF-I gene.[J].2002,11(3).
- [13]Crista M. Carmichael,Matt McGue.A Cross-sectional Examination of Height, Weight, and Body Mass Index in Adult Twins[J].1995,50A(4).
- [14]Walenkamp MJ,Wit JM.Genetic disorders in the growth hormone - insulin-like growth factor-I axis.[J].2006,66(5).
- [15]McCarthy A,Gloyn AL,Mitchell SM,etc.A putative functional polymorphism in the IGF-I gene: association studies with type 2 diabetes, adult height, glucose tolerance, and fetal growth in U.K. populations.[J].2002,51(7).
- [16]Godowski P. J.,Leung D. W.,Meacham L. R.,etc.Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism.[J].1989.
- [17]I, Rietveld,J A M J L, Janssen,E F C, van Rossum,etc.A polymorphic CA repeat in the IGF-I gene is associated with gender-specific differences in body height, but has no effect on the secular trend in body height.[J].2004,61(2).