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Objective: To the ISS (idiopathic short stature,ISS),it has a complic beneticbackground, it dues to the interaction of gene and environment. It is the hot spot andthe direction to probe the predisposing genes from chromatosome in current. We studythe effect of GHR(growth hormone receptor, GHR) gene exon 10 SNPs(singlenucleotide polymorphism, SNP) to IGF-1 in blood, and the effect to human growth.Atlast, we identify the correlation between the GHR gene exon 10 SNPs and the ISS.Methods:1. We detect the IGF-1 in blood in case group and control group withradio, receptor assays,the kit is offered by the Tianjin jiuding medical limitedcompany. We do it according to the instruction, and the intraassay coefficient ofvariation is in the bound of our requirement. We contrast the case group and thecontrol group.2. We draw the venous blood of the patients and the healthy children to for DNAextraction. After that,We use 0.8% agarose gel electrophoresis to detect purity ofDNA.3. We design compose the primer as the aimed directly at the view gene, use PCR toamplificate the view gene,and then use the 0.8% agarose gel electrophoresis toidentity the output of PCR.4. Direct sequencing.5. We analysis the result of sequencing, conducted the single nucleotidepolymorphisms(SNPs) and mutation screening of the exon 10. Then We check itwith Hardy-Weingerg law. All the genotypic frequency reach to the genetic balance, and they are representative.6. Using the x~2 to detect the sex difference and genetype and the allelefrequency, using t to detect the age and IGF-1,we describe the OR and 95%CI. Wedetect the difference on IGF-1 in blood during every genetype using F.All the dataare processed using software of SPSS 12.0.Result:1. Screening of the case group The GH in blood of all the patients are normal, thefunction of thyroid is normal, the chromosome is normal, no chronic disease andendocrine disease. There is no difference between the case group and controlgroup in age and sex(P＞0.05).2. The IGF-1 in blood is normal distribution,the mean square is regularity, there isno difference between the case group and the control group(P＞0.05).3. GHR SNPs:We discovered three SNPs on GHR exon 10,they are748A→C(I544L), 437G→T (C440P) and 853A→C (T579P),consisting with NCBI, the591C→T, 601A→C on NCBI are not detected.The allele frequence of every SNPconsist with Hardy-Weinberg law. The heterozygosis of 748A→C (I544L) ismaximum, it is 54.2%,the amino acids of all the SNPs changed.4. The correlation between GHR SNPs and ISS There is no difference ingenotypic frequency and allele frequency on 748SNP(P＞0.05);the genotypicfrequency and allele frequency on 437, 853SNP are different between the casegroup and the control group(P＜0.05).On 437SNP,T allele frequency advanced,andG allele frequency depressed; on 853SNP, A allele frequency advanced,and Callele frequency depressed.5. The correlation between GHR SNPs and IGF-1(1) On 748SNP, in total,there is no difference on IGF-1 in blood during every genetype (p＜0.05).(2) On 437SNP, in total,there is no difference on IGF-1 in blood during everygenetype(P＞0.05).It is different on IGF-1 in blood between GG and GTgenetype(P＜0.05).In case group,it is different on IGF-1 in blood during everygenetype(P＜0.05),it is different on IGF-1 in blood between GG and TTgenetype(P＜0.05),there is no difference on IGF-1 in blood between GG andGT、GT and TT genetype(P＞0.05).(3) On 853SNP, in total,it is different on IGF-1 in blood during everygenetype(P＞0.05).It is different on IGF-1 in blood between AA and CC, ACand CC genetype(P＜0.05),there is no difference on IGF-1 in blood between AAand AC genetype(P＞0.05).In case group,it is different on IGF-1 in blood duringevery genetype(P＜0.05),it is different on IGF-1 in blood between AAand CC、AC and CC genetype(P＜0.05),there is no difference on IGF-1 in blood betweenAA and AC genetype(P＞0.05).In control group,it is different on IGF-1 in bloodduring every genetype(P＜0.05),there is no difference on IGF-1 in blood betweenAC and AA, CC and AA genetype(P＞0.05),it is different on IGF-1 in bloodbetween CC and AC genetype(P＜0.05).Conclusion:1. The IGF-1 can not be the specific diagnosis index of ISS:2. The 748SNP on GHR exon 10 are not concerned with the morbility of ISS.3. The 748SNPs of GHR exon 10 can not affect the level of IGF-1 in blood.4. On 437SNP, GT, TT genetype and T allele frequence is affectable gene of ISS,andGG genetype and Gallele frequence is the protected gene of ISS.5. On 853SNP, AA, AC genetype and A allele frequence is affectable gene ofISS,and CC genetype and C allele frequence is the protected gene of ISS. 6. The 437 and 853SNPs of GHR exon 10 can affect the IGF-1,and then affect thefunction of growth axis.7. In short,GHR SNPs can influence IGF-1,and then influence the function ofgrowth axis,it is may be the risk factor of part ISS.
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