Perez Garrido Natalia, Pujana Matías, Berger Malena, Ramírez Pablo, Guercio Gabriela, Belgorosky Alicia, Marino Roxana
Laboratorio de Biología Molecular Diagnóstico, CONICET, Buenos Aires, Argentina.
Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina.
Medicina (B Aires). 2021;81(4):574-580.
The growth hormone receptor (GHR) mediates the effect of growth hormone (GH) on linear growth and metabolism. In humans, it exists as two isoforms differing by the retention or exclusion of exon 3; a full-length GHR isoform (GHRfl) and the exon 3-deleted isoform (GHRd3). The genotypic frequency of this polymorphism was analyzed in several studies and in different human populations. However scarce information in Argentinean population is available. Associations between GHRd3 and growth have been reported previously. Some studies have shown that the presence of GHRd3 polymorphism might be a potential variant that improves growth response to recombinant human GH (rhGH) therapy in patients born small for gestational age (SGA), among others. However, over the years the results have been controversial and inconclusive. Based on this, it would be proposed that variants at the genomic level are not completely reflected at the mRNA level. Our aim was to evaluate the genotypic frequencies (%) of the GHR gene polymorphism (GHRfl/GHRfl; GHRfl/GHRd3; GHRd3/GHRd3) in normal Argentinean population (n = 94) and SGA patients (n = 65), and the expression of these polymorphisms at mRNA level in the fetal side of placenta tissues was analyzed. In addition, their association with spontaneous postnatal catch-up growth in SGA patients was also evaluated. In this study, we show a significant increment of compensatory growth in small for gestational age children (SGA) associated to the presence of the GHRd3 allele polymorphism. In addition, the expression of GHR in healthy placentas revealed that no alternative splicing mechanism occurs.
生长激素受体（GHR）介导生长激素（GH）对线性生长和代谢的作用。在人类中，它以两种异构体形式存在，这两种异构体因外显子3的保留或缺失而有所不同；一种全长GHR异构体（GHRfl）和外显子3缺失的异构体（GHRd3）。多项研究在不同人群中分析了这种多态性的基因型频率。然而，关于阿根廷人群的信息却很少。此前已有报道称GHRd3与生长之间存在关联。一些研究表明，GHRd3多态性的存在可能是一种潜在变异，可改善小于胎龄儿（SGA）等患者对重组人生长激素（rhGH）治疗的生长反应。然而，多年来结果一直存在争议且尚无定论。基于此，有人提出基因组水平的变异在mRNA水平上并未完全体现出来。我们的目的是评估正常阿根廷人群（n = 94）和SGA患者（n = 65）中GHR基因多态性（GHRfl/GHRfl；GHRfl/GHRd3；GHRd3/GHRd3）的基因型频率（%）并分析胎盘组织胎儿侧这些多态性在mRNA水平的表达。此外，还评估了它们与SGA患者出生后自发追赶生长的关联。在本研究中，我们发现与GHRd3等位基因多态性的存在相关联，小于胎龄儿（SGA）的代偿性生长显著增加。此外，健康胎盘中GHR的表达显示未发生可变剪接机制。
