Ilhan Muzaffer, Kahraman Ozlem Timirci, Turan Saime, Turgut Seda, Karaman Ozcan, Zeybek Umit, Shukurov Samir, Yaylim Ilhan, Tasan Ertugrul
Bezmialem University, Department of Endocrinology and Metabolism, Vatan Caddesi, 34093 Istanbul, Turkey.
The Institute of Experimental Medicine, Department of Molecular Medicine, Millet Caddesi, Capa, Istanbul University, Istanbul, Turkey.
Ann Endocrinol (Paris). 2015 Oct;76(5):614-9. doi: 10.1016/j.ando.2015.08.005. Epub 2015 Oct 26.
Genetic alterations explaining the clinical variability of prolactinomas still could not be clarified and dopamine D2 receptor (DRD2) polymorphism is a putative candidate for the variable response to dopaminergic treatment. The present study was conducted to investigate the influence of DRD2 TaqI A polymorphism on initial and follow-up characteristics of prolactinoma.
Seventy-two patients with prolactinoma and 98 age and gender matched control subjects were recruited to the case-control study. Serum prolactin levels were assessed by enzyme-linked immunosorbent assay and DRD2 polymorphism was determined by polymerase chain reaction and restriction length polymorphism analysis.
Decrease of prolactin levels and the tumor shrinkage after cabergoline treatment were 93.9±5.9% and 58.3±33.1% in microadenomas and 96.1±6.1% and 51.7±29.3 in macroadenomas (P=0.02 and P>0.05, respectively). We observed no significant difference for DRD2 genotypes and the alleles between the patients and healthy group (P>0.05). Prolactin levels before treatment were correlated with tumor diameter before and after treatment and the percentage of prolactin decrease with treatment (P<0.001 r=0.58, P<0.001 r=0.40 and P<0.001 r=0.47, respectively). Tumor diameter before the treatment was also correlated with the tumor diameter after the treatment (P<0.001 r=0.64) and the percentage of prolactin decrease (P=0.01 r=0.30). However, no significant association was found between characteristics of prolactinoma and DRD2 genotypes and alleles (P>0.05).
This study revealed that DRD2 TaqI A receptor polymorphism was not associated with the development of prolactinoma and its clinical characteristics. Future studies are needed to clarify the clinical implications of genetic alterations in prolactinoma.
解释催乳素瘤临床变异性的基因改变仍未明确，多巴胺D2受体（DRD2）多态性是多巴胺能治疗反应可变的一个假定候选因素。本研究旨在探讨DRD2 TaqI A多态性对催乳素瘤初始及随访特征的影响。
72例催乳素瘤患者及98例年龄和性别匹配的对照者被纳入病例对照研究。采用酶联免疫吸附测定法评估血清催乳素水平，通过聚合酶链反应和限制性片段长度多态性分析确定DRD2多态性。
卡麦角林治疗后，微腺瘤的催乳素水平下降和肿瘤缩小分别为93.9±5.9%和58.3±33.1%，大腺瘤分别为96.1±6.1%和51.7±29.3（P分别为0.02和P>0.05）。我们观察到患者组与健康组之间的DRD2基因型和等位基因无显著差异（P>0.05）。治疗前催乳素水平与治疗前后肿瘤直径以及治疗后催乳素下降百分比相关（P均<0.001，r分别为0.58、0.40和0.47）。治疗前肿瘤直径也与治疗后肿瘤直径相关（P<0.001，r=0.64）以及催乳素下降百分比相关（P=0.01，r=0.30）。然而，未发现催乳素瘤特征与DRD2基因型和等位基因之间存在显著关联（P>0.05）。
本研究表明DRD2 TaqI A受体多态性与催乳素瘤的发生及其临床特征无关。需要进一步研究以阐明催乳素瘤基因改变的临床意义。
