Variants of genes encoding TNF receptors and ligands and proteins regulating TNF activation in familial multiple sclerosis.
Variants of genes encoding TNF receptors and ligands and proteins regulating TNF activation in familial multiple sclerosis.
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DOI：
10.1111/cns.13456
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发表时间：
2020-11
影响因子：
5.5
通讯作者：
Matías-Guiu J
中科院分区：
文献类型：
--
作者：
Torre-Fuentes L;Matías-Guiu JA;Pytel V;Montero-Escribano P;Maietta P;Álvarez S;Gómez-Pinedo U;Matías-Guiu J
许多遗传变异与多发性硬化症（MS）的易感性有关。本研究的目的是确定这些基因的变异是否与MS的高风险相关。我们使用全外显子组测序研究了来自19个家族的116名个体的TNF - α受体和配体的编码基因，以及促进TNF - α表达的蛋白质，其中包括至少两名MS患者。我们比较了多发性硬化症患者、其他自身免疫性疾病患者和健康个体。与一般人群相比，家族性多发性硬化症家族中几个基因的多态性更大；这可能反映了对自身免疫性疾病的易感性。系谱分析还显示，LT‐α变异rs1041981和rs2229094以及LT‐β变异rs4647197与MS相关，而LT‐β变异rs4647183与其他自身免疫性疾病相关。自身免疫性疾病与TNFAIP2变异rs1132339之间的关联尤其值得注意，正如TNFAIP6变异rs1046668似乎遵循隐性遗传模式一样。我们的研究结果支持家族性MS的风险与信号通路变异相关的观点，包括那些涉及TNF‐α的信号通路。影响TNF - α的途径参与免疫信号传导。对19个家族的116名成员进行了全外显子组测序，其中包括至少2名多发性硬化症患者。在TNF‐α通路中发现了几个非同义变体。这些发现支持了家族性MS风险与TNF - α信号通路变异相关的观点。
Numerous genetic variants have been associated with susceptibility to multiple sclerosis (MS). Variants located in genes involved in specific pathways, such as those affecting TNF‐α, can contribute to the risk of MS. The purpose of this study was to determine whether variants of these genes are associated with greater risk of MS. We used whole‐exome sequencing to study genes coding for TNF‐α receptors and ligands, and proteins promoting TNF‐α expression in 116 individuals from 19 families including at least two MS patients. We compared patients with MS, patients with other autoimmune diseases, and healthy individuals. Greater polymorphism was observed in several genes in families with familial MS compared to the general population; this may reflect greater susceptibility to autoimmune diseases. Pedigree analysis also revealed that LT‐α variants rs1041981 and rs2229094 and LT‐β variant rs4647197 were associated with MS and that LT‐β variant rs4647183 was associated with other autoimmune diseases. The association between autoimmune disease and TNFAIP2 variant rs1132339 is particularly noteworthy, as is the fact that TNFAIP6 variant rs1046668 appears to follow a recessive inheritance pattern. Our findings support the idea that the risk of familial MS is associated with variants of signaling pathways, including those involving TNF‐α. Pathways affecting TNF‐α are involved in immune signaling. Whole‐exome sequencing in 116 members of 19 families including at least two patients with multiple sclerosis was performed. Several nonsynonymous variants in TNF‐α pathways were found. The findings support the idea that the risk of familial MS is associated with variants of TNF‐α signaling pathways.
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影响因子：
17.1
作者：
Housley WJ;Fernandez SD;Vera K;Murikinati SR;Grutzendler J;Cuerdon N;Glick L;De Jager PL;Mitrovic M;Cotsapas C;Hafler DA
通讯作者：
Hafler DA
影响因子：
3.2
作者：
Saeed M
通讯作者：
Saeed M
影响因子：
3.1
作者：
Aktas, Orhan;Schulze-Topphoff, Ulf;Zipp, Frauke
通讯作者：
Zipp, Frauke
DOI：
10.1073/pnas.1117347108
发表时间：
2011-12-06
影响因子：
11.1
作者：
Zula, Joana A.;Green, Holly C.;van Boxel-Dezaire, Anette H. H.
通讯作者：
van Boxel-Dezaire, Anette H. H.
影响因子：
30.8
作者：
Kircher, Martin;Witten, Daniela M.;Jain, Preti;O'Roak, Brian J.;Cooper, Gregory M.;Shendure, Jay
通讯作者：
Shendure, Jay