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. 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. 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. 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.

中文翻译：

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5-HTTLPR 和 SLE 疾病状态对静息态脑功能的相互作用

系统性红斑狼疮（SLE）的神经精神受累是一种常见的临床表现。在 SLE 患者中，脑功能是中枢神经系统损伤的更敏感的预测因子，并且脑功能异常可能在出现实质性神经精神症状之前就很明显。5-羟色胺 (5-HT) 系统能够与中枢神经系统 (CNS) 中的大多数神经化学系统相互作用，影响大脑功能。血清素转运蛋白基因连锁多态性区域（5-HTTLPR）是5-HT系统基因多态性的重要元件，与5-羟色胺转运蛋白（5-HTT）基因表达的控制直接相关。SLE 患者的 5-HTTLPR 与功能性脑测量之间的关系需要更多的研究，因为它是揭示神经精神性狼疮病理生理学的最具吸引力的成像遗传学目标之一。收集了 51 名无明显神经精神表现的 SLE 患者和 44 名健康志愿者的静息态功能磁共振成像 (rs-fMRI) 图像。选择区域均匀性（ReHo）、低频波动幅度（ALFF）和低频波动分数幅度（fALFF）作为评估脑功能的指标。根据解剖自动标记模板，将灰质分为116个区域。提取各脑区的平均ReHo值、平均ALFF值、平均fALFF值。采用聚合酶链式反应和琼脂糖凝胶电泳检测所有研究对象的5-HTTLPR基因型。采用双向协方差分析来研究 SLE 疾病状态和 5-HTTLPR 基因型对静息态脑功能是否存在交互作用。在具有 S/S 纯合性的 SLE 患者中，与健康对照相比，在右顶叶、下角回和右侧中央旁小叶中观察到的平均 ReHo、平均 ALFF 和平均 fALFF 值显着较低。然而，这种区别在 L 等位基因携带者中并不明显。在 S/S 基因型中，与 HC 组相比，SLE 患者左后扣带回平均 ReHo 降低，左尾状核平均 fALFF 降低，左颞极（颞上回）平均 ALFF 降低。相反，L 等位基因携带者之间没有发现此类差异。值得注意的是，在 L 等位基因携带者中，与 HC 组相比，SLE 患者的右侧海马平均 ReHo 值较高，而与 HC 组相比，左侧内侧回和副扣带回的平均 ALFF 值较低。相反，这些差异在 S/S 纯合子中并不明显。右侧顶叶、下角回和右侧中央旁小叶的脑功能受到 SLE 疾病状态和 5-HTTLPR 基因型交互作用的影响。