HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders.
HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders.
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DOI：
10.1038/s41598-021-97140-7
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发表时间：
2021-09-08
影响因子：
4.6
通讯作者：
Tamouza R
中科院分区：
文献类型：
--
作者：
Le Clerc S;Lombardi L;Baune BT;Amare AT;Schubert KO;Hou L;Clark SR;Papiol S;Cearns M;Heilbronner U;Degenhardt F;Tekola-Ayele F;Hsu YH;Shekhtman T;Adli M;Akula N;Akiyama K;Ardau R;Arias B;Aubry JM;Backlund L;Bhattacharjee AK;Bellivier F;Benabarre A;Bengesser S;Biernacka JM;Birner A;Brichant-Petitjean C;Cervantes P;Chen HC;Chillotti C;Cichon S;Cruceanu C;Czerski PM;Dalkner N;Dayer A;Del Zompo M;DePaulo JR;Étain B;Jamain S;Falkai P;Forstner AJ;Frisen L;Frye MA;Fullerton JM;Gard S;Garnham JS;Goes FS;Grigoroiu-Serbanescu M;Grof P;Hashimoto R;Hauser J;Herms S;Hoffmann P;Jiménez E;Kahn JP;Kassem L;Kuo PH;Kato T;Kelsoe JR;Kittel-Schneider S;Ferensztajn-Rochowiak E;König B;Kusumi I;Laje G;Landén M;Lavebratt C;Leckband SG;Tortorella A;Manchia M;Martinsson L;McCarthy MJ;McElroy SL;Colom F;Millischer V;Mitjans M;Mondimore FM;Monteleone P;Nievergelt CM;Nöthen MM;Novák T;O'Donovan C;Ozaki N;Ösby U;Pfennig A;Potash JB;Reif A;Reininghaus E;Rouleau GA;Rybakowski JK;Schalling M;Schofield PR;Schweizer BW;Severino G;Shilling PD;Shimoda K;Simhandl C;Slaney CM;Pisanu C;Squassina A;Stamm T;Stopkova P;Maj M;Turecki G;Vieta E;Veeh J;Witt SH;Wright A;Zandi PP;Mitchell PB;Bauer M;Alda M;Rietschel M;McMahon FJ;Schulze TG;Spadoni JL;Boukouaci W;Richard JR;Le Corvoisier P;Barrau C;Zagury JF;Leboyer M;Tamouza R
双相情感障碍（BD）是一种严重的精神疾病，锂（Li）是急性和维持治疗的金标准。在BD中对Li的治疗反应是异质性的，仍然需要允许患者分层的可靠生物标志物。由国际锂遗传学联盟（ConLiGen）进行的GWAS最近在人类白细胞抗原（HLA）区域中鉴定了与锂治疗反应相关的遗传标记。为了更好地理解这种关联的分子机制，我们对ConLiGen队列的欧洲患者的HLA区域的经典等位基因进行了遗传学估算。我们发现属于HLA-DRB 1 *11：01经典等位基因的氨基酸变体的最佳信号，与对Li的更好反应相关（p < 1 × 10−3;隐性模型中FDR < 0.09）。HLA-DRB 1重链74位的丙氨酸或亮氨酸与良好反应相关，而精氨酸或谷氨酸与不良反应相关。由于这些变体与常见的炎症/自身免疫过程有关，我们的研究结果强烈表明，HLA介导的低炎症背景可能有助于BD患者对Li的有效反应，而炎症状态压倒Li抗炎特性将有利于弱反应。
Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.
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DOI：
10.1016/s0140-6736(16)00143-4
发表时间：
2016-03-12
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hou L;Heilbronner U;Degenhardt F;Adli M;Akiyama K;Akula N;Ardau R;Arias B;Backlund L;Banzato CEM;Benabarre A;Bengesser S;Bhattacharjee AK;Biernacka JM;Birner A;Brichant-Petitjean C;Bui ET;Cervantes P;Chen GB;Chen HC;Chillotti C;Cichon S;Clark SR;Colom F;Cousins DA;Cruceanu C;Czerski PM;Dantas CR;Dayer A;Étain B;Falkai P;Forstner AJ;Frisén L;Fullerton JM;Gard S;Garnham JS;Goes FS;Grof P;Gruber O;Hashimoto R;Hauser J;Herms S;Hoffmann P;Hofmann A;Jamain S;Jiménez E;Kahn JP;Kassem L;Kittel-Schneider S;Kliwicki S;König B;Kusumi I;Lackner N;Laje G;Landén M;Lavebratt C;Leboyer M;Leckband SG;Jaramillo CAL;MacQueen G;Manchia M;Martinsson L;Mattheisen M;McCarthy MJ;McElroy SL;Mitjans M;Mondimore FM;Monteleone P;Nievergelt CM;Nöthen MM;Ösby U;Ozaki N;Perlis RH;Pfennig A;Reich-Erkelenz D;Rouleau GA;Schofield PR;Schubert KO;Schweizer BW;Seemüller F;Severino G;Shekhtman T;Shilling PD;Shimoda K;Simhandl C;Slaney CM;Smoller JW;Squassina A;Stamm T;Stopkova P;Tighe SK;Tortorella A;Turecki G;Volkert J;Witt S;Wright A;Young LT;Zandi PP;Potash JB;DePaulo JR;Bauer M;Reininghaus EZ;Novák T;Aubry JM;Maj M;Baune BT;Mitchell PB;Vieta E;Frye MA;Rybakowski JK;Kuo PH;Kato T;Grigoroiu-Serbanescu M;Reif A;Del Zompo M;Bellivier F;Schalling M;Wray NR;Kelsoe JR;Alda M;Rietschel M;McMahon FJ;Schulze TG
通讯作者：
Schulze TG
影响因子：
7.3
作者：
Mamedov, Azad;Vorobyeva, Nadezhda;Belogurov, Alexey, Jr.
通讯作者：
Belogurov, Alexey, Jr.
影响因子：
4.6
作者：
Malhi, Gin S.;Bassett, Darryl;Singh, Ajeet B.
通讯作者：
Singh, Ajeet B.
直径疾病反映了进化基因的权衡：精神病学，神经病学，风湿病，肿瘤学和免疫学的证据。
DOI：
10.1093/emph/eov021
发表时间：
2015-09-09
期刊：
Evolution, medicine, and public health
影响因子：
--
作者：
Crespi BJ;Go MC
通讯作者：
Go MC
影响因子：
3.4
作者：
Kaimen-Maciel, Damacio Ramon;Vissoci Reiche, Edna Maria;Donadi, Eduardo Antonio
通讯作者：
Donadi, Eduardo Antonio