自閉症スペクトラム障害患者における脂質過酸化の役割

The role of lipid peroxidation in individuals with autism spectrum disorders.

• Kunio Yui
• George Imataka
• Hitomi Sasaki
• Ryoichi Shiroki

抄録

自閉症スペクトラム障害（ASD）の病態生理における酸化LDLであるマロンジアルデヒド修飾低密度リポ蛋白（MDA-LDL）の役割は不明である。我々は、ASD患者11名と年齢をマッチさせた健常者7名を対象に、MDA-LDLと行動症状との関連を検討した。行動症状は異常行動チェックリスト（ABC）を用いて評価した。本研究ではサンプル数が少ないため、第1に、予測精度と解釈可能性を高めるための適応Lassoの採用、第2に、血漿中の変数の適切な選択のための変動係数の計算、第3に、血漿中の変数の良い候補の選択の3つの対策を行った。血漿中のMDA-LDL、エイコサペンタエン酸、ドコサヘキサエン酸（DHA）、DHA/アラキドン酸比はASD群で有意に高く、血漿中のスーパーオキシドジスムターゼ（SOD）レベルは対照群に比べて有意に低かった。総ABCスコアはASD群が対照群に比べて有意に高かった。重回帰分析および適応ラッソ法により、血漿DHA値の増加とABCスコアの合計値および血漿MDA-LDL値の増加との関連が明らかになった。このようなDHAと血漿MDA-LDLレベルの関連は、ASD患者の行動に寄与している可能性がある。

The role of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidized LDL, in the pathophysiology of autism spectrum disorder (ASD) is unclear. We studied association between MDA-LDL and behavioral symptoms in 11 individuals with ASD and 7 age -matched normal controls. Behavioral symptoms were assessed using the Aberrant Behavior Checklists (ABC). Because small sample size in this study, three measures were conducted: first, employment of adaptive Lasso for enhancing the accuracy of prediction and interpretability; second, calculation of coefficient of variation for an appropriate selection of plasma variables; and third, selection of good candidates of plasma variables. Plasma levels of MDA-LDL, eicosapentaenoic acid, docosahexaenoic acid (DHA) and DHA/arachidonic acid ratios were significantly higher, while plasma superoxide dismutase (SOD) levels were significantly lower in the ASD group than in the control group. The total ABC scores were significantly higher in the ASD group than in the control group. Multiple linear regression analysis and the adaptive Lasso revealed association of increased plasma DHA levels with the ABC total scores and increased plasma MDA-LDL levels. Such association between DHA and plasma MDA-LDL levels may contribute to behavior in individuals with ASD.