Gender-specific effects of genetic variants within Th1 and Th17 cell-mediated immune response genes on the risk of developing rheumatoid arthritis.
Gender-specific effects of genetic variants within Th1 and Th17 cell-mediated immune response genes on the risk of developing rheumatoid arthritis.
复制标题
DOI：
10.1371/journal.pone.0072732
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sainz J
中科院分区：
文献类型：
--
作者：
Cáliz R;Canet LM;Lupiañez CB;Canhão H;Escudero A;Filipescu I;Segura-Catena J;Soto-Pino MJ;Expósito-Ruiz M;Ferrer MÁ;García A;Romani L;González-Utrilla A;Vallejo T;Pérez-Pampin E;Hemminki K;Försti A;Collantes E;Fonseca JE;Sainz J
本研究旨在探讨Th 1和Th 17细胞介导的免疫应答基因的单核苷酸多态性（SNPs）是否对女性和男性类风湿关节炎（RA）的风险有不同的影响。在第一阶段，在458例RA患者和512名对照中，对C型凝集素和MCP-1/CCR 2轴的27个功能/标签多态性进行了基因分型。Dectin-2 rs 4264222 T等位基因携带者患RA的风险增加（OR = 1.47，95%CI 1.10-1.96），而携带DC-SIGN rs 4804803 G、MCP-1 rs 1024611 G、MCP-1 rs 13900 T和MCP-1 rs 4586 C等位基因的患者患RA的风险降低（OR = 0.66，95%CI 0.49-0.88; OR = 0.66，95%CI 0.50-0.89; OR = 0.73，95%CI 0.55-0.97和OR = 0.68，95%CI 0.51-0.91）。 有趣的是，在Dectin-2 rs 4264222和Dectin-2 rs7134303中观察到显著的性别特异性差异：携带Dectin-2 rs 4264222 T和Dectin-2 rs7134303 G等位基因的女性患RA的风险增加（OR = 1.93，95%CI 1.34-2.79和OR = 1.90，95%CI 1.29-2.80）。 此外，其他5个SNP仅与一种性别显著相关：携带MCP-1 rs 1024611 G、MCP-1 rs 13900 T和MCP-1 rs 4586 C等位基因的女性患RA的风险降低（OR = 0.61，95%CI 0.43-0.87; OR = 0.67，95%CI 0.47-0.95和OR = 0.60，95%CI 0.42-0.86）。 在男性中，DC-SIGN rs 2287886 A等位基因携带者患RA的风险增加（OR = 1.70，95%CI 1.03-2.78），而DC-SIGN rs 4804803 G等位基因携带者患RA的风险降低（OR = 0.53，95%CI 0.32-0.89）。 在第2阶段，我们对754名RA患者和519名对照者的这些SNP进行了基因分型，导致合并样本中Dectin-2 rs 4264222、MCP-1 rs 1024611、MCP-1 rs 13900和DC-SIGN rs 4804803多态性的一致性别特异性相关性（OR = 1.38，95%CI 1.08-1.77; OR = 0.74，95%CI 0.58-0.94; OR = 0.76，95%CI 0.59-0.97和OR = 0.56，95%CI 0.34-0.93）。 显著SNP的SNP-SNP相互作用分析也显示了在女性中未观察到的显著的两位点相互作用模型。该模型由Dectin-2 rs 4264222和Dectin-2 rs7134303 SNP组成，并表明变体之间存在协同效应。这些研究结果表明，Dectin-2，MCP-1和DC-SIGN多态性可能，至少部分，占性别相关的差异，对RA的易感性。
The present study was conducted to explore whether single nucleotide polymorphisms (SNPs) in Th1 and Th17 cell-mediated immune response genes differentially influence the risk of rheumatoid arthritis (RA) in women and men. In phase one, 27 functional/tagging polymorphisms in C-type lectins and MCP-1/CCR2 axis were genotyped in 458 RA patients and 512 controls. Carriers of Dectin-2 rs4264222T allele had an increased risk of RA (OR = 1.47, 95%CI 1.10–1.96) whereas patients harboring the DC-SIGN rs4804803G, MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of developing the disease (OR = 0.66, 95%CI 0.49–0.88; OR = 0.66, 95%CI 0.50–0.89; OR = 0.73, 95%CI 0.55–0.97 and OR = 0.68, 95%CI 0.51–0.91). Interestingly, significant gender-specific differences were observed for Dectin-2 rs4264222 and Dectin-2 rs7134303: women carrying the Dectin-2 rs4264222T and Dectin-2 rs7134303G alleles had an increased risk of RA (OR = 1.93, 95%CI 1.34–2.79 and OR = 1.90, 95%CI 1.29–2.80). Also five other SNPs showed significant associations only with one gender: women carrying the MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased risk of RA (OR = 0.61, 95%CI 0.43–0.87; OR = 0.67, 95%CI 0.47–0.95 and OR = 0.60, 95%CI 0.42–0.86). In men, carriers of the DC-SIGN rs2287886A allele had an increased risk of RA (OR = 1.70, 95%CI 1.03–2.78), whereas carriers of the DC-SIGN rs4804803G had a decreased risk of developing the disease (OR = 0.53, 95%CI 0.32–0.89). In phase 2, we genotyped these SNPs in 754 RA patients and 519 controls, leading to consistent gender-specific associations for Dectin-2 rs4264222, MCP-1 rs1024611, MCP-1 rs13900 and DC-SIGN rs4804803 polymorphisms in the pooled sample (OR = 1.38, 95%CI 1.08–1.77; OR = 0.74, 95%CI 0.58–0.94; OR = 0.76, 95%CI 0.59–0.97 and OR = 0.56, 95%CI 0.34–0.93). SNP-SNP interaction analysis of significant SNPs also showed a significant two-locus interaction model in women that was not seen in men. This model consisted of Dectin-2 rs4264222 and Dectin-2 rs7134303 SNPs and suggested a synergistic effect between the variants. These findings suggest that Dectin-2, MCP-1 and DC-SIGN polymorphisms may, at least in part, account for gender-associated differences in susceptibility to RA.
登录
查看更多内容
影响因子：
6.7
作者：
Gringhuis SI;Wevers BA;Kaptein TM;van Capel TM;Theelen B;Boekhout T;de Jong EC;Geijtenbeek TB
通讯作者：
Geijtenbeek TB
影响因子：
3.9
作者：
Dieguez-Gonzalez, Rebeca;Akar, Servet;Gonzalez, Antonio
通讯作者：
Gonzalez, Antonio
影响因子：
--
作者：
AKAHOSHI, T;WADA, C;MATSUSHIMA, K
通讯作者：
MATSUSHIMA, K
影响因子：
30.5
作者：
Gringhuis, Sonja I.;den Dunnen, Jeroen;Geijtenbeek, Teunis B. H.
通讯作者：
Geijtenbeek, Teunis B. H.
影响因子：
4.3
作者：
Carter, Robert W.;Thompson, Clare;Tough, David F.
通讯作者：
Tough, David F.