Interaction of 5-HTTLPR and SLE disease status on resting-state brain function
Abstract Background Neuropsychiatric involvement in systemic lupus erythematosus (SLE) is a common clinical manifestation. In SLE patients, cerebral function is a more sensitive predictor of central nervous system damage, and abnormalities in cerebral function may be apparent before substantial neur...
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BMC
2024-01-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-024-03276-y |
| _version_ | 1797273672559362048 |
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| author | Lihua Ma Yifan Yang Shu Li Bibhuti Upreti Shuang Liu Xiangyu Wang Ru Bai Yuqi Cheng Jian Xu |
| author_facet | Lihua Ma Yifan Yang Shu Li Bibhuti Upreti Shuang Liu Xiangyu Wang Ru Bai Yuqi Cheng Jian Xu |
| author_sort | Lihua Ma |
| collection | DOAJ |
| description | Abstract Background Neuropsychiatric involvement in systemic lupus erythematosus (SLE) is a common clinical manifestation. In SLE patients, cerebral function is a more sensitive predictor of central nervous system damage, and abnormalities in cerebral function may be apparent before substantial neuropsychiatric symptoms occur. The 5-hydroxynyptamine(5-HT) system has the ability to interact with the majority of the neurochemical systems in the central nervous system (CNS), influencing brain function. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) is an essential element of the 5-HT system gene polymorphism and is directly related to the control of 5-hydroxytryptamine transporter (5-HTT)gene expression. The relationship between 5-HTTLPR and functional brain measurements in SLE patients requires more investigation because it is one of the most attractive imaging genetics targets for shedding light on the pathophysiology of neuropsychiatric lupus. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) images were collected from 51 SLE patients without obvious neuropsychiatric manifestations and 44 healthy volunteers. Regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) were selected as indicators for evaluating brain function. In accordance with the Anatomical Automatic Labeling template, the gray matter was divided into 116 regions. The mean ReHo value, mean ALFF value, and mean fALFF value of each brain region were extracted. 5-HTTLPR genotypes of all research objects were tested by polymerase chain reaction and agarose gel electrophoresis. Two-way analysis of covariance was used to investigate whether there is an interaction effect between SLE disease status and 5-HTTLPR genotype on resting-state brain function. Results In SLE patients with S/S homozygosity, there were notably lower mean ReHo, mean ALFF, and mean fALFF values observed in the right parietal, inferior angular gyrus, and the right paracentral lobule compared to healthy controls. However, this distinction was not evident among carriers of the L allele. Within the S/S genotype, SLE patients exhibited decreased mean ReHo in the left posterior cingulate gyrus, reduced mean fALFF in the left caudate nucleus, and diminished mean ALFF in the left temporal pole: superior temporal gyrus, in contrast to the HC group. Conversely, no such differences were discerned among carriers of the L allele. Notably, among L allele carriers, SLE patients displayed a higher mean ReHo value in the right hippocampus compared to the HC group, while demonstrating a lower mean ALFF value in the left medial and paracingulate gyrus in contrast to the HC group. Conversely, these differences were not apparent among S/S homozygotes. Conclusions Brain function in the right parietal and inferior angular gyrus and the right paracentral lobule is affected by the interaction effect of SLE disease status and 5-HTTLPR genotype. |
| first_indexed | 2024-03-07T14:47:42Z |
| format | Article |
| id | doaj.art-76c4a23db08c4e4bb3860bda72a35bea |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-03-07T14:47:42Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
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| series | Arthritis Research & Therapy |
| spelling | doaj.art-76c4a23db08c4e4bb3860bda72a35bea2024-03-05T19:51:51ZengBMCArthritis Research & Therapy1478-63622024-01-012611910.1186/s13075-024-03276-yInteraction of 5-HTTLPR and SLE disease status on resting-state brain functionLihua Ma0Yifan Yang1Shu Li2Bibhuti Upreti3Shuang Liu4Xiangyu Wang5Ru Bai6Yuqi Cheng7Jian Xu8Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityDepartment of Psychiatry, First Affiliated Hospital of Kunming Medical UniversityDepartment of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical UniversityAbstract Background Neuropsychiatric involvement in systemic lupus erythematosus (SLE) is a common clinical manifestation. In SLE patients, cerebral function is a more sensitive predictor of central nervous system damage, and abnormalities in cerebral function may be apparent before substantial neuropsychiatric symptoms occur. The 5-hydroxynyptamine(5-HT) system has the ability to interact with the majority of the neurochemical systems in the central nervous system (CNS), influencing brain function. Serotonin transporter gene-linked polymorphic region (5-HTTLPR) is an essential element of the 5-HT system gene polymorphism and is directly related to the control of 5-hydroxytryptamine transporter (5-HTT)gene expression. The relationship between 5-HTTLPR and functional brain measurements in SLE patients requires more investigation because it is one of the most attractive imaging genetics targets for shedding light on the pathophysiology of neuropsychiatric lupus. Methods Resting-state functional magnetic resonance imaging (rs-fMRI) images were collected from 51 SLE patients without obvious neuropsychiatric manifestations and 44 healthy volunteers. Regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional amplitude of low-frequency fluctuations (fALFF) were selected as indicators for evaluating brain function. In accordance with the Anatomical Automatic Labeling template, the gray matter was divided into 116 regions. The mean ReHo value, mean ALFF value, and mean fALFF value of each brain region were extracted. 5-HTTLPR genotypes of all research objects were tested by polymerase chain reaction and agarose gel electrophoresis. Two-way analysis of covariance was used to investigate whether there is an interaction effect between SLE disease status and 5-HTTLPR genotype on resting-state brain function. Results In SLE patients with S/S homozygosity, there were notably lower mean ReHo, mean ALFF, and mean fALFF values observed in the right parietal, inferior angular gyrus, and the right paracentral lobule compared to healthy controls. However, this distinction was not evident among carriers of the L allele. Within the S/S genotype, SLE patients exhibited decreased mean ReHo in the left posterior cingulate gyrus, reduced mean fALFF in the left caudate nucleus, and diminished mean ALFF in the left temporal pole: superior temporal gyrus, in contrast to the HC group. Conversely, no such differences were discerned among carriers of the L allele. Notably, among L allele carriers, SLE patients displayed a higher mean ReHo value in the right hippocampus compared to the HC group, while demonstrating a lower mean ALFF value in the left medial and paracingulate gyrus in contrast to the HC group. Conversely, these differences were not apparent among S/S homozygotes. Conclusions Brain function in the right parietal and inferior angular gyrus and the right paracentral lobule is affected by the interaction effect of SLE disease status and 5-HTTLPR genotype.https://doi.org/10.1186/s13075-024-03276-ySystemic lupus erythematosus5-HTTLPRResting-state functional magnetic resonance imaging |
| spellingShingle | Lihua Ma Yifan Yang Shu Li Bibhuti Upreti Shuang Liu Xiangyu Wang Ru Bai Yuqi Cheng Jian Xu Interaction of 5-HTTLPR and SLE disease status on resting-state brain function Arthritis Research & Therapy Systemic lupus erythematosus 5-HTTLPR Resting-state functional magnetic resonance imaging |
| title | Interaction of 5-HTTLPR and SLE disease status on resting-state brain function |
| title_full | Interaction of 5-HTTLPR and SLE disease status on resting-state brain function |
| title_fullStr | Interaction of 5-HTTLPR and SLE disease status on resting-state brain function |
| title_full_unstemmed | Interaction of 5-HTTLPR and SLE disease status on resting-state brain function |
| title_short | Interaction of 5-HTTLPR and SLE disease status on resting-state brain function |
| title_sort | interaction of 5 httlpr and sle disease status on resting state brain function |
| topic | Systemic lupus erythematosus 5-HTTLPR Resting-state functional magnetic resonance imaging |
| url | https://doi.org/10.1186/s13075-024-03276-y |
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