Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia
BACKGROUND: Schizophrenia is a severe mental disorder with high heritability, and cognitive dysfunction is one of the core features. Growing evidence suggests the genetic risk of schizophrenia may contribute to cognitive impairments. The variant rs1635 (nucleotide sequence: c.455C>A; amino ac...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.941171/full |
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| author | Yang Yang Yi Su Guiming Wei Zhewei Kang Zhe Lu Yundan Liao Tianlan Lu Hao Yan Weihua Yue Weihua Yue Weihua Yue Ying Qin Yuyanan Zhang |
| author_facet | Yang Yang Yi Su Guiming Wei Zhewei Kang Zhe Lu Yundan Liao Tianlan Lu Hao Yan Weihua Yue Weihua Yue Weihua Yue Ying Qin Yuyanan Zhang |
| author_sort | Yang Yang |
| collection | DOAJ |
| description | BACKGROUND: Schizophrenia is a severe mental disorder with high heritability, and cognitive dysfunction is one of the core features. Growing evidence suggests the genetic risk of schizophrenia may contribute to cognitive impairments. The variant rs1635 (nucleotide sequence: c.455C>A; amino acid sequence: T152N) located on the (NFKB activating protein like) NKAPL gene confers risk for schizophrenia and might play a role in the neurodevelopmental process, which is particularly relevant to cognitive function. However, the relationship between rs1635 and cognitive function remains unclear.METHODS: A total of 130 patients with early-onset schizophrenia (EOS) and 300 patients with adult-onset schizophrenia (AOS) of Han Chinese were recruited and underwent neurocognitive tests by using the MATRICS Consensus Cognitive Battery (MCCB). The NKAPL rs1635 was genotyped by using DNA sequencing. The peripheral blood NKAPL mRNA expression level was examined in 152T or 152N carriers (n = 20) in EOS patients, by using the qRT-PCR. The phosphorylation level of NAKPL T152N polymorphism was detected by cell experiments. In utero electroporation of mouse embryos was examined to explore the effect of Nkapl on neuronal migration.RESULTS: Compared with rs1635 AA and AC carriers, CC (the CC genotype encodes the protein NKAPL-152T) carriers of EOS patients performed better in cognitive domain of speed of processing (t = 2.644, p = 0.009), trail making test (t = 2.221, p = 0.028) and category fluency (t = 2.578, p = 0.011). However, patients with AOS exhibited no significant differences in seven domains among the three genotype groups. There were no significant differences in cognitive performance between EOS and AOS. In EOS patients, NKAPL mRNA level in NKAPL-152N carriers is significantly lower than that of NKAPL-152T carriers. The phosphorylation level of NKAPL-152N is significantly decreased compared to NKAPL-152T. In utero electroporation showed that Nkapl deletion impairs the embryonic radial migration process.CONCLUSION: The present study found that NKAPL rs1635 was associated with cognitive impairments and peripheral blood mRNA expression level in EOS patients. The NKAPL full-length protein is required for embryonic cortical neuronal migration. The phosphorylation level of NKAPL-152N is significantly decreased. The NKAPL T152N may affect the NAKPL mRNA expression level and embryonic cortical neuronal migration by regulating the NAKPL protein phosphorylation. These data suggest that NKAPL rs1635 affects cognitive function by regulating early brain development in early-onset schizophrenia. |
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| spelling | doaj.art-765ec34fe20c469c83b04e57f08d0b592022-12-22T02:33:53ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-06-011310.3389/fgene.2022.941171941171Association of NKAPL rs1635 With Cognitive Function in Early-Onset SchizophreniaYang Yang0Yi Su1Guiming Wei2Zhewei Kang3Zhe Lu4Yundan Liao5Tianlan Lu6Hao Yan7Weihua Yue8Weihua Yue9Weihua Yue10Ying Qin11Yuyanan Zhang12Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, ChinaPeking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, ChinaDepartment of Neurology, Shandong Daizhuang Hospital, Jining, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, ChinaPKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, ChinaChinese Institute for Brain Research, Beijing, ChinaThe Second People’s Hospital of Guizhou Province, Guiyang, ChinaPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, ChinaBACKGROUND: Schizophrenia is a severe mental disorder with high heritability, and cognitive dysfunction is one of the core features. Growing evidence suggests the genetic risk of schizophrenia may contribute to cognitive impairments. The variant rs1635 (nucleotide sequence: c.455C>A; amino acid sequence: T152N) located on the (NFKB activating protein like) NKAPL gene confers risk for schizophrenia and might play a role in the neurodevelopmental process, which is particularly relevant to cognitive function. However, the relationship between rs1635 and cognitive function remains unclear.METHODS: A total of 130 patients with early-onset schizophrenia (EOS) and 300 patients with adult-onset schizophrenia (AOS) of Han Chinese were recruited and underwent neurocognitive tests by using the MATRICS Consensus Cognitive Battery (MCCB). The NKAPL rs1635 was genotyped by using DNA sequencing. The peripheral blood NKAPL mRNA expression level was examined in 152T or 152N carriers (n = 20) in EOS patients, by using the qRT-PCR. The phosphorylation level of NAKPL T152N polymorphism was detected by cell experiments. In utero electroporation of mouse embryos was examined to explore the effect of Nkapl on neuronal migration.RESULTS: Compared with rs1635 AA and AC carriers, CC (the CC genotype encodes the protein NKAPL-152T) carriers of EOS patients performed better in cognitive domain of speed of processing (t = 2.644, p = 0.009), trail making test (t = 2.221, p = 0.028) and category fluency (t = 2.578, p = 0.011). However, patients with AOS exhibited no significant differences in seven domains among the three genotype groups. There were no significant differences in cognitive performance between EOS and AOS. In EOS patients, NKAPL mRNA level in NKAPL-152N carriers is significantly lower than that of NKAPL-152T carriers. The phosphorylation level of NKAPL-152N is significantly decreased compared to NKAPL-152T. In utero electroporation showed that Nkapl deletion impairs the embryonic radial migration process.CONCLUSION: The present study found that NKAPL rs1635 was associated with cognitive impairments and peripheral blood mRNA expression level in EOS patients. The NKAPL full-length protein is required for embryonic cortical neuronal migration. The phosphorylation level of NKAPL-152N is significantly decreased. The NKAPL T152N may affect the NAKPL mRNA expression level and embryonic cortical neuronal migration by regulating the NAKPL protein phosphorylation. These data suggest that NKAPL rs1635 affects cognitive function by regulating early brain development in early-onset schizophrenia.https://www.frontiersin.org/articles/10.3389/fgene.2022.941171/fullNKAPLrs1635early-onset schizophreniacognitive functionneuron migration |
| spellingShingle | Yang Yang Yi Su Guiming Wei Zhewei Kang Zhe Lu Yundan Liao Tianlan Lu Hao Yan Weihua Yue Weihua Yue Weihua Yue Ying Qin Yuyanan Zhang Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia Frontiers in Genetics NKAPL rs1635 early-onset schizophrenia cognitive function neuron migration |
| title | Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia |
| title_full | Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia |
| title_fullStr | Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia |
| title_full_unstemmed | Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia |
| title_short | Association of NKAPL rs1635 With Cognitive Function in Early-Onset Schizophrenia |
| title_sort | association of nkapl rs1635 with cognitive function in early onset schizophrenia |
| topic | NKAPL rs1635 early-onset schizophrenia cognitive function neuron migration |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.941171/full |
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