Department of Human Genetics, National Institute of Mental Health and Neurosciences.
Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, and Departments of.
Psychiatr Genet. 2022 Aug 1;32(4):146-155. doi: 10.1097/YPG.0000000000000315. Epub 2022 Mar 31.
T helper 17 (Th17) pathway has been reported to be abnormal in schizophrenia; however, it is not known whether variation within genes of this pathway has any impact on schizophrenia. Herein, the impact of genetic variations and gene-gene interactions of Th17 pathway-related genes on the risk, psychopathology, and brain volume was examined in schizophrenia patients.
Functional polymorphisms within interleukin 6 ( IL6 )(rs1800795 and rs1800797), IL10 (rs1800872 and rs1800896), IL17A (rs2275913 and rs8193036), IL22 (rs2227484 and rs2227485), IL23R (rs1884444), and IL27 (rs153109 and rs181206) genes were studied in 224 schizophrenia patients and 226 healthy controls. These variants were correlated with the brain morphometry, analyzed using MRI in a subset of patients ( n = 117) and controls ( n = 137).
Patients carrying CC genotype of rs2227484 of IL22 gene had significantly higher apathy total score [ F (1,183) = 5.60; P = 0.019; partial ɳ 2 = 0.030]. Significant epistatic interactions between IL6 (rs1800797) and IL17A (rs2275913) genes were observed in schizophrenia patients. GG genotype of rs2275913 of IL17A gene was associated with reduced right middle occipital gyrus volume in schizophrenia patients ( T = 4.56; P < 0.001).
Interactions between genes of Th17 pathway impact the risk for schizophrenia. The variants of Th17 pathway-related genes seem to have a determining effect on psychopathology and brain morphometric changes in schizophrenia.
Th17 途径已被报道在精神分裂症中异常；然而，尚不清楚该途径基因内的变异是否会对精神分裂症产生任何影响。在此，研究了 Th17 途径相关基因的遗传变异和基因-基因相互作用对精神分裂症患者的风险、精神病理学和脑容量的影响。
白细胞介素 6（IL6）（rs1800795 和 rs1800797）、IL10（rs1800872 和 rs1800896）、IL17A（rs2275913 和 rs8193036）、IL22（rs2227484 和 rs2227485）、IL23R（rs1884444）和 IL27（rs153109 和 rs181206）基因中的功能性多态性在 224 例精神分裂症患者和 226 例健康对照者中进行了研究。在一组患者（n=117）和对照组（n=137）中，使用 MRI 对这些变体与脑形态进行了相关性分析。
携带 IL22 基因 rs2227484 CC 基因型的患者，冷漠总分明显较高[F（1,183）=5.60；P=0.019；偏 ɳ 2=0.030]。在精神分裂症患者中观察到 IL6（rs1800797）和 IL17A（rs2275913）基因之间存在显著的上位性相互作用。IL17A 基因 rs2275913 的 GG 基因型与精神分裂症患者右侧中枕叶体积减少有关（T=4.56；P<0.001）。
Th17 途径基因的相互作用影响精神分裂症的风险。Th17 途径相关基因的变体似乎对精神分裂症的精神病理学和脑形态变化有决定性影响。
