目的探讨抗精神病药物在治疗精神分裂症患者过程中出现的体重增加与5羟色胺2C受体(HTR2C)基因启动子区-759C/T(rs3813929)单核苷酸多态性的关系。方法在Pubmed、Springer、China biology medicine disc(CBM)、谷歌学术、万方数据库等检...目的探讨抗精神病药物在治疗精神分裂症患者过程中出现的体重增加与5羟色胺2C受体(HTR2C)基因启动子区-759C/T(rs3813929)单核苷酸多态性的关系。方法在Pubmed、Springer、China biology medicine disc(CBM)、谷歌学术、万方数据库等检索1990~2017年精神分裂症患者中有关HTR2C-759C/T基因多态性与抗精神病药物诱导的体重增加关联性研究的文献,对-759C/T位点(CT+TT)/CC,(CT+CC)/TT基因型进行Meta分析。用RevMan version5.3计算OR值及95%可信区间,并按人种因素作亚组分析。结果共有20篇文献符合纳入标准,经Meta分析发现HTR2C-759T与抗精神病药物引发的体重增加呈显著负相关[(CT+TT)/CCOR=0.42,95%CI(0.26~0.66),P=0.0002]。亚组分析中,高加索人群和东亚人群含HTR2C-759T患者的体重增加占比人数显著低于CC基因型患者(高加索人群OR=0.48,95%CI(0.26~0.88),P=0.020,东亚人群OR=0.34,95%CI(0.17~0.69),P=0.002)。HTR2C-759C与抗精神病药物引发的体重增加有正相关趋势[(CT+CC)/TTOR=2.29,95%CI(1.00~5.23),P=0.05]。亚组分析中高加索人群[OR=2.58,95%CI(0.61~10.94),P=0.200]和东亚人群(OR=2.13,95%CI(0.78~5.86),P=0.14)结论一致,差异无统计学意义(P>0.05)。结论HTR2C基因启动子-759C/T单核苷酸多态性与抗精神病药物导致的患者体重增加相关联,携带HTR2C-759T可能是限制体重增加的保护因子。展开更多
Pulmonary fibrosis(PF)is sexually dimorphic,with a relatively high prevalence and severity in males;however,the mechanism remains unclear.Our study revealed pronounced sexual dimorphism of immune cell genes in the lun...Pulmonary fibrosis(PF)is sexually dimorphic,with a relatively high prevalence and severity in males;however,the mechanism remains unclear.Our study revealed pronounced sexual dimorphism of immune cell genes in the lung,among which grancalcin(GCA)showed profound sex differences.GCA was produced by lung-infiltrating bone marrow macrophages triggered by heightened inflammation in the lung.However,a unique HTR2C+alveolar macrophage population enriched in female lungs metabolically reprogramed bone marrow-derived macrophages and constrained local GCA amplification.As a novel chemokine,GCA bound to protein tyrosine phosphatase receptor type T(PTPRT)in Th17 cells and facilitated pathogenic lung infiltration by activating the ROCK1-MLC pathway,thus aggravating lung fibrosis.Notably,both GCA and Th17 cells abundantly accumulated in lung biopsies from male PF patients but not in those from female patients.GCA-neutralizing antibodies in combination with pirfenidone,a prescribed medication for treating fibrosis,provided superior effectiveness and survival rates against PF compared with treatment with pirfenidone alone.Overall,our findings reveal that sex-biased lung fibrosis is shaped by lung immuneregulatory units,which could be targeted to limit lung fibrosis.展开更多
文摘目的探讨抗精神病药物在治疗精神分裂症患者过程中出现的体重增加与5羟色胺2C受体(HTR2C)基因启动子区-759C/T(rs3813929)单核苷酸多态性的关系。方法在Pubmed、Springer、China biology medicine disc(CBM)、谷歌学术、万方数据库等检索1990~2017年精神分裂症患者中有关HTR2C-759C/T基因多态性与抗精神病药物诱导的体重增加关联性研究的文献,对-759C/T位点(CT+TT)/CC,(CT+CC)/TT基因型进行Meta分析。用RevMan version5.3计算OR值及95%可信区间,并按人种因素作亚组分析。结果共有20篇文献符合纳入标准,经Meta分析发现HTR2C-759T与抗精神病药物引发的体重增加呈显著负相关[(CT+TT)/CCOR=0.42,95%CI(0.26~0.66),P=0.0002]。亚组分析中,高加索人群和东亚人群含HTR2C-759T患者的体重增加占比人数显著低于CC基因型患者(高加索人群OR=0.48,95%CI(0.26~0.88),P=0.020,东亚人群OR=0.34,95%CI(0.17~0.69),P=0.002)。HTR2C-759C与抗精神病药物引发的体重增加有正相关趋势[(CT+CC)/TTOR=2.29,95%CI(1.00~5.23),P=0.05]。亚组分析中高加索人群[OR=2.58,95%CI(0.61~10.94),P=0.200]和东亚人群(OR=2.13,95%CI(0.78~5.86),P=0.14)结论一致,差异无统计学意义(P>0.05)。结论HTR2C基因启动子-759C/T单核苷酸多态性与抗精神病药物导致的患者体重增加相关联,携带HTR2C-759T可能是限制体重增加的保护因子。
基金supported by the National Natural Science Foundation of China(Grant Nos.82170866 and 82422016 to HYZ,82401013 to JW,and 82430028 to XHL)the Natural Science Foundation of Hunan Province,China(Grant No.2024JJ2095 to HYZ,2025JJ60561 to JW)+1 种基金the Changsha City Outstanding Innovative Youth Development Program(Grant No.Kq2306007 to HYZ)the Scientific Research Program of FuRong Laboratory(Grant No.2024PT5104 to XHL).
文摘Pulmonary fibrosis(PF)is sexually dimorphic,with a relatively high prevalence and severity in males;however,the mechanism remains unclear.Our study revealed pronounced sexual dimorphism of immune cell genes in the lung,among which grancalcin(GCA)showed profound sex differences.GCA was produced by lung-infiltrating bone marrow macrophages triggered by heightened inflammation in the lung.However,a unique HTR2C+alveolar macrophage population enriched in female lungs metabolically reprogramed bone marrow-derived macrophages and constrained local GCA amplification.As a novel chemokine,GCA bound to protein tyrosine phosphatase receptor type T(PTPRT)in Th17 cells and facilitated pathogenic lung infiltration by activating the ROCK1-MLC pathway,thus aggravating lung fibrosis.Notably,both GCA and Th17 cells abundantly accumulated in lung biopsies from male PF patients but not in those from female patients.GCA-neutralizing antibodies in combination with pirfenidone,a prescribed medication for treating fibrosis,provided superior effectiveness and survival rates against PF compared with treatment with pirfenidone alone.Overall,our findings reveal that sex-biased lung fibrosis is shaped by lung immuneregulatory units,which could be targeted to limit lung fibrosis.
