{"id":6207,"date":"2023-02-17T06:56:42","date_gmt":"2023-02-17T06:56:42","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2017-purinergic-receptors-p2rx4-and-p2rx7-in-familial-multiple-sclerosis\/"},"modified":"2023-02-17T06:56:43","modified_gmt":"2023-02-17T06:56:43","slug":"2017-purinergic-receptors-p2rx4-and-p2rx7-in-familial-multiple-sclerosis","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2017-purinergic-receptors-p2rx4-and-p2rx7-in-familial-multiple-sclerosis\/","title":{"rendered":"2017 &#8211; Purinergic receptors P2RX4 and P2RX7 in familial multiple sclerosis"},"content":{"rendered":"<p>Genetic variants in the purinergic receptors\u00a0P2RX4\u00a0and\u00a0P2RX7\u00a0have been shown to affect susceptibility to multiple sclerosis (MS). In this study, we set out to evaluate whether rare coding variants of major effect could also be identified in these purinergic receptors. Sequencing analysis of\u00a0P2RX4\u00a0and\u00a0P2RX7\u00a0in 193 MS patients and 100 controls led to the identification of a rare three variant haplotype (P2RX7\u00a0rs140915863:C>T [p.T205M],\u00a0P2RX7\u00a0rs201921967:A>G [p.N361S], and\u00a0P2RX4\u00a0rs765866317:G>A [p.G135S]) segregating with disease in a multi-incident family with six family members diagnosed with MS (logarithm of odds = 3.07). Functional analysis of this haplotype in HEK293 cells revealed impaired P2X7 surface expression (P\u00a0< 0.01), resulting in over 95% inhibition of adenosine triphosphate (ATP)-induced pore function (P\u00a0< 0.001) and a marked reduction in phagocytic ability (P\u00a0< 0.05). In addition, transfected cells showed 40% increased peak ATP-induced inward current (P\u00a0< 0.01), and a greater Ca<sup>2+<\/sup>\u00a0response to the P2X4 135S variant compared with wild type (P\u00a0< 0.0001). Our study nominates rare genetic variants in\u00a0P2RX4\u00a0and\u00a0P2RX7\u00a0as major genetic contributors to disease, further supporting a role for these purinergic receptors in MS and the disruption of transmembrane cation channels leading to impairment of phagocytosis as the pathological mechanisms of disease.\n<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50],"therapeutic_areas":[],"target_categories":[337],"target_families":[358],"targets":[226,277],"resource_keyword":[],"class_list":["post-6207","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","target_categories-ligand-gated-ion-channels","target_families-p2x-receptors","targets-p2x7","targets-p2x4"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6207","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6207"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6207"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6207"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6207"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6207"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6207"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6207"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6207"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6207"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}