Gao Ming, Zhu Bin, Xu Zhe, Liu Shujun, Liu Jiajia, Zhang Guojun, Gao Yang, Fan Yubo, Kang Xixiong
Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
Beijing Engineering Research Center of Immunological Reagents and Clinical Research, Beijing, 100050, China.
BMC Med Genet. 2018 Oct 5;19(1):182. doi: 10.1186/s12881-018-0698-2.
It has been reported that the single nucleotide polymorphism (SNP) rs2854744 at the - 202 locus of insulin-like growth factor binding protein-3 (IGFBP3) is associated with serum levels and a number of malignancies. However, the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in the current study, we aimed to investigate whether the -202A/C polymorphism of IGFBP3 constitutes a risk factor for acromegaly.
The study included 102 acromegalic patients and 143 control subjects in Beijing Tiantan Hospital. The genotyping of IGFBP3 was carried out using the MassARRAY method. Serum IGFBP3 concentrations were also determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations of genetic polymorphisms with the development of acromegaly and its different subtypes.
The study revealed that the C allele of rs2854744 was associated with a reduced risk of acromegaly (OR 0.594, 95% CI 0.388-0.909), as well as with the female (OR 0.385, 95% CI 0.206-0.72), macroadenoma (OR 0.557, 95% CI 0.347-0.893) and monotherapy (OR 0.512, 95% CI 0.316-0.828) subgroups under the additive model. A higher serum IGFBP3 level was observed in patients with the AA genotype, but this difference was not significant (P = 0.331).
This study is one of the first to show that the IGFBP3 polymorphism may have an influence on serum levels and that the C allele of rs2854744 is associated with a reduced risk of acromegaly. This correlation was more prominent in females, those with large tumours and those treated with monotherapy in a Chinese population. Genetic polymorphism of IGFBP3 may be involved in the development of acromegaly.
据报道，胰岛素样生长因子结合蛋白3（IGFBP3）-202位点的单核苷酸多态性（SNP）rs2854744与血清水平及多种恶性肿瘤相关。然而，IGFBP3基因多态性对肢端肥大症的影响尚不清楚。因此，在本研究中，我们旨在探究IGFBP3基因-202A/C多态性是否构成肢端肥大症的危险因素。
本研究纳入了北京天坛医院的102例肢端肥大症患者和143例对照者。采用MassARRAY方法对IGFBP3进行基因分型。同时测定血清IGFBP3浓度。采用优势比（OR）和95%置信区间（CI）评估基因多态性与肢端肥大症及其不同亚型发生之间的关联。
研究显示，rs2854744的C等位基因与肢端肥大症风险降低相关（OR 0.594，95% CI 0.388 - 0.909），在加性模型下，还与女性（OR 0.385，95% CI 0.206 - 0.72）、大腺瘤（OR 0.557，95% CI 0.347 - 0.893）及单药治疗（OR 0.512，95% CI 0.316 - 0.828）亚组相关。AA基因型患者的血清IGFBP3水平较高，但差异无统计学意义（P = 0.331）。
本研究首次表明IGFBP3基因多态性可能影响血清水平，且rs2854744的C等位基因与肢端肥大症风险降低相关。在中国人群中，这种相关性在女性、肿瘤较大者及接受单药治疗者中更为显著。IGFBP3基因多态性可能参与了肢端肥大症的发生发展。
