Bone and body composition response to testosterone therapy vary according to polymorphisms in the CYP19A1 gene.
Bone and body composition response to testosterone therapy vary according to polymorphisms in the CYP19A1 gene.
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DOI：
10.1007/s12020-019-02008-6
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发表时间：
2019-09
期刊：
影响因子：
3.7
通讯作者：
Armamento-Villareal R
中科院分区：
文献类型：
--
作者：
Aguirre LE;Colleluori G;Robbins D;Dorin R;Shah VO;Chen R;Jan IZ;Qualls C;Villareal DT;Armamento-Villareal R
目的：探讨CYP19A1基因单核苷酸多态性（snp）对睾酮治疗反应及对副作用易感性的影响。这是一项前瞻性单臂研究，受试者为晨间血清睾酮水平低（<10.68 nmol/l）的男性，每2周肌肉注射一次cypionate睾酮200 mg，持续18个月。我们用双能x线吸收仪测量了面骨矿物质密度（aBMD）和身体组成，用外周定量计算机断层扫描测量了胫骨体积骨密度和几何形状，用酶联免疫吸附法测量了骨转换标志物，用液相色谱/质谱法测量了睾酮和雌二醇，用微阵列进行了基因分型，用定量聚合酶链反应测量了CYP19A1表达，用红细胞压积和前列腺特异性抗原（PSA）测量了CYP19A1表达。我们招募了105名男性（40-74岁）。snp rs1062033和rs700518在18个月时的结果存在显著差异。与CG和CC基因型相比，GG基因型rs1062033的全身aBMD显著升高，但胫骨骨大小显著降低。体组成分析表明，CC基因型rs1062033和AA基因型rs700518的总瘦体重和尾瘦体重分别显著高于CG和GG、AG和GG。rs700518的GG基因型显著增加PSA (GG=105.8±23.3% vs. AG+AA=53.4±11.3%,p=0.046)，而不同基因型的红细胞压积变化具有可比性。CYP19A1在两种snp中均以GG基因型表达最高。我们首次证明了CYP19A1 snp影响性腺功能低下男性对睾酮治疗的反应，强调了基因谱在治疗中的重要性，即使是在常见的临床条件下。
To evaluate the influence of single nucleotide polymorphisms (SNPs) of CYP19A1 on the response and susceptibility to side effects from testosterone therapy. This is a prospective, single-arm study of men with low morning serum testosterone (<10.68 nmol/l) administered testosterone cypionate 200 mg intramuscularly every 2 weeks for 18 months. We measured areal bone mineral density (aBMD) and body composition by dual energy x-ray absorptiometry, tibial volumetric BMD and geometry by peripheral quantitative computer tomography, bone turnover markers by enzyme-linked immunosorbent assay, testosterone and estradiol by liquid-chromatography/mass-spectroscopy, genotyping by microarray, CYP19A1 expression by quantitative polymerase chain reaction, hematocrit and prostate-specific antigen (PSA). We enrolled 105 men (40–74 years old). SNPs rs1062033 and rs700518 were associated with significant differences in outcomes at 18 months. The GG genotype in rs1062033 had significant increase in whole body aBMD, but had significant decrease in tibial bone size compared to the CG and CC genotypes. Body composition analysis showed that the CC genotype of rs1062033, and the AA genotype of rs700518, had significant increases in total lean and appendicular lean mass compared to CG and GG, and AG and GG, respectively. The GG genotype of rs700518 had significant increase in PSA (GG=105.8±23.3% vs. AG+AA=53.4±11.3%, p=0.046) while hematocrit changes were comparable among genotypes. CYP19A1 expression was highest in GG genotype in both SNPs. For the first time, we demonstrated that CYP19A1 SNPs influence response to testosterone therapy in hypogonadal men, highlighting the importance of genetic profiling in therapeutics even for common clinical conditions.
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影响因子：
5.8
作者：
Barrett-Connor, E;Mueller, JE;Sartoris, DJ
通讯作者：
Sartoris, DJ
影响因子：
4.4
作者：
DEVLIN, B;RISCH, N
通讯作者：
RISCH, N
影响因子：
4
作者：
Armamento-Villareal, R.;Aguirre, L.;Villareal, D. T.
通讯作者：
Villareal, D. T.
影响因子：
3.7
作者：
Dimitriadis, Georgios K.;Randeva, Harpal S.;Barber, Thomas M.
通讯作者：
Barber, Thomas M.
DOI：
10.26355/eurrev_201803_14559
发表时间：
2018-03-01
影响因子：
3.3
作者：
He, Y.;Wang, C. -L.
通讯作者：
Wang, C. -L.