Jajodia Ajay, Kaur Harpreet, Kumari Kalpana, Kanojia Neha, Gupta Meenal, Baghel Ruchi, Sood Mamta, Jain Sanjeev, Chadda Rakesh K, Kukreti Ritushree
Genomics and Molecular Medicine CSIR-Institute of Genomics and Integrative Biology Mall Road Delhi 110007 India.
Department of Psychiatry All India Institute of Medical Sciences Ansari Nagar New Delhi 110029 India.
Mol Genet Genomic Med. 2015 Aug 9;4(1):18-27. doi: 10.1002/mgg3.169. eCollection 2016 Jan.
Neurodevelopmental and neuroimmunological genes critically regulate antipsychotic treatment outcome. We report genetic associations of antipsychotic response in 742 schizophrenia patients from Indian populations of Indo-European and Dravidian ancestry, segregated by disease severity. Meta-analysis comparing the two populations identified CCL2 [rs4795893: OR (95% CI) = 1.79 (1.27-2.52), P = 7.62 × 10(-4); rs4586: OR (95% CI) = 1.74 (1.24-2.43), P = 1.13 × 10(-3)] and GRIA4 [rs2513265: OR (95% CI) = 0.53 (0.36-0.78), P = 1.44 × 10(-3)] in low severity group; and, ADCY2 [rs1544938: OR (95% CI) = 0.36 (0.19-0.65), P = 7.68 × 10(-4)] and NRG1 [rs13250975, OR (95% CI) = 0.42 (0.23-0.79), P = 6.81 × 10(-3); rs17716295, OR (95% CI) = 1.78 (1.15-2.75), P = 8.71 × 10(-3)] in high severity group, with incomplete response toward antipsychotics. To our knowledge, this is the first study to identify genetic polymorphisms associated with the efficacy of antipsychotic treatment of schizophrenia patients from two major India populations.
神经发育和神经免疫基因对精神分裂症治疗结果起着关键的调节作用。我们报告了来自印欧语系和达罗毗荼语系印度人群的742例精神分裂症患者抗精神病药物反应的基因关联，这些患者按疾病严重程度进行了分类。对这两个人群进行的荟萃分析发现，在低严重程度组中，CCL2基因（rs4795893：比值比[95%可信区间]=1.79[1.27 - 2.52]，P = 7.62×10⁻⁴；rs4586：比值比[95%可信区间]=1.74[1.24 - 2.43]，P = 1.13×10⁻³）和GRIA4基因（rs2513265：比值比[95%可信区间]=0.53[0.36 - 0.78]，P = 1.44×10⁻³）与抗精神病药物反应有关；在高严重程度组中，ADCY2基因（rs1544938：比值比[95%可信区间]=0.36[0.19 - 0.65]，P = 7.68×10⁻⁴）和NRG1基因（rs13250975，比值比[95%可信区间]=0.42[0.23 - 0.79]，P = 6.81×10⁻³；rs17716295，比值比[95%可信区间]=1.78[1.15 - 2.75]，P = 8.71×10⁻³）与对抗精神病药物反应不完全有关。据我们所知，这是第一项鉴定出与来自印度两大人群的精神分裂症患者抗精神病药物治疗疗效相关基因多态性的研究。
