Ghrelin水平及基因多态性与GHD患儿心脏病变的相关性研究

Relationships of Ghrelin Levels and Gene Polymorphisms to Cardiac Abnormalities in Children with Growth Hormone Deficiency

目的分析生长激素缺乏症(GHD)患儿的Ghrelin的水平及基因多态性与患儿心脏病变的相关性。方法收集65例GHD患儿为GHD组,50例健康体检儿童为对照组。经三维斑点追踪成像超声技术(3D-STI)检测2组的心脏结构和功能指标,包括整体纵行应变(GLS)、整体径向应变(GRS)、整体圆周应变(GCS)、整体扭转角度(GTA)和左室体质量(LVM));ELISA法检测2组血浆的acyl-Ghrelin、desacyl-Ghrelin水平,计算总Ghrelin及acyl-Ghrelin/desacyl-Ghrelin(A/D)值;PCR-RFLP法检测C408A和G346A位点单核苷酸多态性。结果与对照组比较,GHD组的GLS、GRS、GCS、LVM均明显降低(P<0.05或P<0.01),但2组的GTA比较差异无统计学意义(P>0.05);GHD组的acyl-Ghrelin、desacyl-Ghrelin、总Ghrelin水平及A/D值均高于对照组(均P<0.01);GHD组的acyl-Ghrelin、desacyl-Ghrelin水平、总Ghrelin水平与GLS、GRS、GCS均呈负相关(r=-0.548,P=0.001;r=-0.481,P=0.003;r=-0.411,P=0.014;r=-0.520,P=0.001;r=-0.444,P=0.007;r=-0.381,P=0.024;r=-0.536,P=0.001;r=-0.464,P=0.005;r=-0.397,P=0.018),而与GTA、LVM均无相关性(P>0.05);A/D值与GLS、GRS、GCS、GTA、LVM均无相关性(P>0.05);与对照组比较,GHD组GG基因型分布较对照组高(χ2=8.851,P=0.003),GT基因型分布较对照组低(χ2=11.523,P=0.001),CC、CT、TT比较差异均无统计学意义(均P>0.05);GHD组不同基因型对应的GLS、GRS、GCS、GTA、LVM检测值比较差异均无统计学意义(均P>0.05)。结论GHD患儿存在心脏的结构和功能改变,且acyl-Ghrelin、desacyl-Ghrelin、总Ghrelin的水平与心脏的功能改变相关;Ghrelin的C408A基因多态性与GHD的发病相关。

Objective To analyze the relationships of ghrelin levels and gene polymorphisms to cardiac abnormalities in children with growth hormone deficiency(GHD).Methods Cardiac structure and function were detected by three-dimensional cardiac ultrasound speckle tracking imaging(3D-STI)in 65 GHD children and 50 healthy controls,including global longitudinal strain(GLS),global circumferential strain(GCS),global radial strain(GRS)global torsion angle(GTA)and left ventricular mass(LVM).Plasma levels of acyl-ghrelin and desacyl-ghrelin were measured by ELISA to calculate the total ghrelin levels and acyl-ghrelin and desacyl-ghrelin(A/D)ratio.The single nucleotide polymorphisms at C408A and G346A loci were determined by PCR-RFLP.Results Compared with control group,the values of GLS,GRS,GCS and LVM decreased,but the levels of acyl-ghrelin,desacyl-ghrelin,total ghrelin and A/D ratio increased in GHD group(P<0.05 or P<0.01).There was no significant difference in the GTA between the two groups(P>0.05).In GHD group,the levels of acyl-ghrelin,desacyl-ghrelin and total ghrelin were negatively related to the values of GLS,GRS and GCS(r=-0.548,P=0.001;r=-0.481,P=0.003;r=-0.411,P=0.014;r=-0.520,P=0.001;r=-0.444,P=0.007;r=-0.381,P=0.024;r=-0.536,P=0.001;r=-0.464,P=0.005;r=-0.397,P=0.018;respectively),but not correlated with the values of GTA and LVM(P>0.05).Furthermore,the ratio of A/D was not associated with the values of GLS,GRS,GCS,GTA and LVM(P>0.05).The distribution of GG genotype in GHD group was higher than that in control group(χ2=8.851,P=0.003).However,the distribution of GT genotype in GHD group was lower than that in control group(χ2=11.523,P=0.001).No statistical differences were found in the distribution of CC,CT and TT genotypes between the two groups(P>0.05).In GHD group,there were no statistical differences in the values of GLS,GRS,GCS,GTA and LVM among different genotypes(P>0.05).Conclusion There are obvious changes in cardiac structure and function in children with GHD.The levels of acyl-ghrelin,desacyl-ghrelin and total ghrelin are correlated with cardiac function,and C408A polymorphism of ghrelin is related to the onset of GHD.