Role of ZBTB38 Genotype and Expression in Growth and Response to Recombinant Human Growth Hormone Treatment.
Role of ZBTB38 Genotype and Expression in Growth and Response to Recombinant Human Growth Hormone Treatment.
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DOI：
10.1210/jendso/bvac006
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发表时间：
2022-03-01
影响因子：
4.1
通讯作者：
Murray PG
中科院分区：
文献类型：
--
作者：
Parsons S;Stevens A;Whatmore A;Clayton PE;Murray PG
ZBTB38基因的单核苷酸多态(SNPs)与特发性矮小(ISS)和成人身高相关。本研究旨在(A)通过ZBTB38SNP基因分析ISS患者的表型及其对重组人生长激素(RhGH)的反应；(B)描述ZBTB38的表达与正常生长的关系；(C)描述ZBTB38基因敲除对细胞增殖和MCM10表达的影响。研究了261例ISS患者rs6764769和rs724016的基因分型与表型的关系，并对93例接受重组人生长激素治疗的患者进行了基因分型。对87例正常儿童和青壮年的ZBTB38表达与年龄的关系进行了研究。用siRNAs敲除ZBTB38在SiHA细胞中的表达，并用WST-8法检测细胞增殖。我们发现rs6764769和rs724016处于连锁不平衡状态。Rs724016GG基因携带者出生时身长较低(P SDS0.01)，身高 = 变化较小(P = 0.02)。ZBTB 38的表达与年龄呈正相关(P <； 0.001)。SiRNA介导的ZBTB38基因敲除后72小时和96小时细胞增殖增加，但不改变MCM10的表达。与ISS相关的ZBTB38内的SNPs与ISS患者队列中较高的出生尺寸和对rhGH治疗的更好反应有关，而ZBTB38的表达与年龄呈正相关。
Single-nucleotide polymorphisms (SNPs) in ZBTB38 have been associated with idiopathic short stature (ISS) and adult height. This study sought to (a) characterize the phenotype of ISS patients and their response to recombinant human growth hormone (rhGH) by ZBTB38 SNP genotype; (b) describe the relationship of ZBTB38 expression with normal growth; and (c) describe the in vitro effects of ZBTB38 knockdown on cell proliferation and MCM10 expression. The genotype-phenotype relationship of rs6764769 and rs724016 were explored in 261 ISS patients and effects of genotype on response to rhGH were assessed in 93 patients treated with rhGH. The relationship between age and ZBTB38 expression was assessed in 87 normal children and young adults. Knockdown of ZBTB38 in SiHA cells was achieved with siRNAs and cell proliferation assessed with a WST-8 assay. We found that rs6764769 and rs724016 are in linkage disequilibrium. The rs724016 GG genotype was associated with lower birth length (P = 0.01) and a lower change in height SDS over the first year of treatment (P = 0.02). ZBTB38 expression was positively correlated with age (P < 0.001). siRNA-mediated knockdown of ZBTB38 resulted in increased cell proliferation at 72 and 96 hours posttransfection but did not alter expression of MCM10. SNPs within ZBTB38 associated with ISS are linked to higher birth size within a cohort of ISS patients and a better response to rhGH therapy while ZBTB38 expression is positively related to age.
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影响因子：
3.5
作者：
Yengo, Loic;Sidorenko, Julia;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
DOI：
10.1038/gim.2017.159
发表时间：
2018-06
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Hauer NN;Popp B;Schoeller E;Schuhmann S;Heath KE;Hisado-Oliva A;Klinger P;Kraus C;Trautmann U;Zenker M;Zweier C;Wiesener A;Abou Jamra R;Kunstmann E;Wieczorek D;Uebe S;Ferrazzi F;Büttner C;Ekici AB;Rauch A;Sticht H;Dörr HG;Reis A;Thiel CT
通讯作者：
Thiel CT
影响因子：
3.5
作者：
Okada, Yukinori;Kamatani, Yoichiro;Kamatani, Naoyuki
通讯作者：
Kamatani, Naoyuki
影响因子：
8.8
作者：
Miotto, Benoit;Chibi, Moredreck;Defossez, Pierre-Antoine
通讯作者：
Defossez, Pierre-Antoine
影响因子：
6.2
作者：
Marchal C;de Dieuleveult M;Saint-Ruf C;Guinot N;Ferry L;Olalla Saad ST;Lazarini M;Defossez PA;Miotto B
通讯作者：
Miotto B