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中国汉族人群中VEGF与VDR基因-基因及基因-吸烟相互作用与多发性骨髓瘤风险的关联

Association of VEGF and VDR gene- gene and gene- smoking interaction on risk of multiple myeloma in Chinese Han population.

作者信息

Chen Peng, Du Zhen-Lan, Zhang Yuan, Liu Bing, Guo Zhi, Lou Jin-Xing, He Xue-Peng, Chen Hui-Ren

机构信息

Department of Hematology, PLA Army General Hospital, Beijing, 100700, People's Republic of China.

Department of Hematology and Oncology, Affiliated Bayi Children's Hospital, PLA Army General Hospital, Beijing, 100700, People's Republic of China.

出版信息

Oncotarget. 2017 May 30;8(22):36509-36516. doi: 10.18632/oncotarget.16510.

Abstract

AIMS

To investigate the association of several single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) and vitamin D receptor (VDR) gene polymorphisms and additional gene- gene and gene- smoking interaction with multiple myeloma (MM) risk in Chinese population.

METHODS

Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association between 6 SNPs within VEGF and VDR gene, additional gene- gene and gene- smoking interaction on MM risk.

RESULTS

MM risk is significantly higher in carriers with the rs699947- A allele within VEGF gene than those with CC genotype (CA+ AA versus CC), adjusted OR (95%CI) =1.72 (1.19-2.33), and higher in carriers with rs2228570- T allele within VDR gene than those with CC genotype (CT+ TT versus CC), adjusted OR (95%CI) = 1.68 (1.26-2.17). We also found a significant two-locus model (p=0.0010) involving rs699947 and rs2228570, and a significant two-locus model (p=0.0107) involving rs2228570 andsmoking. Participants with rs699947- CA+AA and rs2228570- CT+TT genotype had the highest MM risk, compared to participants with rs699947- CC and rs2228570- CC genotype, OR (95%CI) = 3.12 (1.82 -4.61). Smokers with rs2228570- CT+TT genotype had the highest MM risk, compared to never- smokers with rs2228570- CC genotype, OR (95%CI) = 3.27 (1.74-4.86).

CONCLUSIONS

We found that the A allele of rs699947 within VEGF and T allele of rs2228570 within VDR gene, interaction between rs699947 and rs2228570, rs2228570 andsmoking were all associated with increased MM risk.

摘要

目的

研究血管内皮生长因子(VEGF)和维生素D受体(VDR)基因内的几个单核苷酸多态性(SNP)以及其他基因-基因和基因-吸烟相互作用与中国人群多发性骨髓瘤(MM)风险的关联。

方法

采用广义多因素降维法(GMDR)筛选SNP与吸烟之间的最佳相互作用组合。进行逻辑回归分析以研究VEGF和VDR基因内的6个SNP、其他基因-基因和基因-吸烟相互作用与MM风险之间的关联。

结果

VEGF基因中携带rs699947 - A等位基因的携带者患MM的风险显著高于CC基因型者(CA + AA与CC相比),校正比值比(95%可信区间)= 1.72(1.19 - 2.33);VDR基因中携带rs2228570 - T等位基因的携带者患MM的风险高于CC基因型者(CT + TT与CC相比),校正比值比(95%可信区间)= 1.68(1.26 - 2.17)。我们还发现一个涉及rs699947和rs2228570的显著两位点模型(p = 0.0010),以及一个涉及rs2228570和吸烟的显著两位点模型(p = 0.0107)。与rs699947 - CC和rs2228570 - CC基因型的参与者相比,rs699947 - CA + AA和rs2228570 - CT + TT基因型的参与者患MM的风险最高,比值比(95%可信区间)= 3.12(1.82 - 4.61)。与rs2228570 - CC基因型的从不吸烟者相比,rs2228570 - CT + TT基因型的吸烟者患MM的风险最高,比值比(95%可信区间)= 3.27(1.74 - 4.86)。

结论

我们发现VEGF基因中rs699947的A等位基因、VDR基因中rs2228570的T等位基因、rs699947与rs2228570之间的相互作用以及rs2228570与吸烟均与MM风险增加相关。

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