The signal transducer and activator of transcription 5B gene polymorphism contributes to the cholesterol metabolism in Japanese children with growth hormone deficiency
The signal transducer and activator of transcription 5B gene polymorphism contributes to the cholesterol metabolism in Japanese children with growth hormone deficiency
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DOI：
10.1111/j.1365-2265.2011.03980.x
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发表时间：
2011-05-01
影响因子：
3.2
通讯作者：
Hara, Toshiro
中科院分区：
文献类型：
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作者：
Makimura, Mika;Ihara, Kenji;Hara, Toshiro
背景与目的GH在脂质代谢中起重要作用.在本研究中，我们专注于JAK 2-信号转导子和转录激活子5（STAT 5）通路，其传递来自GH受体的信号，并选择STAT 5A/B基因作为GH缺乏症（GHD）的脂质代谢调节的候选基因。在开始GH治疗前和治疗后3、6、9和12个月监测血清总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）和非HDL-C水平。在开始GH治疗前和治疗后12个月测量身高、体重、体重指数和血清胰岛素样生长因子-I（IGF-I）水平。对于STAT 5A/B基因的遗传分析，使用HapMap项目主页上的标签SNP选择程序选择5个标签SNP。用荧光素酶法检测STAT 5 B基因-44816A/G SNP的启动子活性。五标签SNP（rs 4029774、rs6503691、rs 9900213、rs 16967637和rs 2272087）挑选STAT 5 A/B基因，遗传学研究表明，在STAT 5 B基因的同一区块中，所分析的SNP的次要等位基因的杂合子或纯合子的儿科GHD患者显示出显著较高的血清TC或非HDL-GH治疗12个月前后的C水平。大多数SNPs也显示了GH治疗12个月期间血清TC或非HDL-C水平降低的基因型之间的显著差异。荧光素酶检测结果显示，STAT 5 B基因中的-44816A/G SNP（rs 4029774）在体外对GHD患儿的胆固醇代谢有一定的影响。
P>Background and aimsGH plays a significant role in the lipid metabolism. In this study, we focused on the JAK2 - signal transducer and activator of the transcription 5 (STAT5) pathway, which transmit the signals from the GH receptor, and selected the STAT5A/B gene as a candidate for the regulation of lipid metabolism in GH deficiency (GHD).Design and participantsThe study population comprised 83 children with idiopathic GHD. The serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and the non-HDL cholesterol (non-HDL-C) levels were monitored before and at 3, 6, 9 and 12 months after starting GH treatment. The height, weight, body mass index, and serum insulin-like growth factor-I (IGF-I) level were also measured before and 12 months after starting the GH treatment. For the genetic analysis of the STAT5A/B gene, five tag SNPs were selected using the tag SNP picker programme on the homepage of the HapMap project. The evaluation of promoter activity of the -44816A/G SNP in the STAT5B gene was performed by a luciferase assay in vitro.ResultsThe TC and non-HDL-C levels were gradually decreased during the GH treatment. Five tag SNPs (rs4029774, rs6503691, rs9900213, rs16967637 and rs2272087) were picked up for the STAT5A/B gene, and the genetic study demonstrated that the paediatric GHD patients who were heterozygotes or homozygotes of minor alleles of the analysed SNPs in the same block of the STAT5B gene showed significantly higher serum TC or non-HDL-C levels both before and after GH treatment for 12 months. Most of the SNPs also demonstrated significant differences among genotypes in the decreases in serum TC or non-HDL-C levels during the 12 months of GH treatment. A luciferase assay showed that the -44816A/G SNP (rs4029774) in the STAT5B gene functionally affected the expression level in vitro.ConclusionThese results indicate that STAT5B may therefore play a role in regulating the cholesterol metabolism in children with GHD.