Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan.
Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan.
Transl Psychiatry. 2024 Oct 14;14(1):435. doi: 10.1038/s41398-024-03141-1.
Recent genome-wide association studies (GWASs) have identified fatty acid desaturase (FADS) genes, which code key enzymes involved in polyunsaturated fatty acid (PUFA) desaturation as susceptibility genes for bipolar disorder (BD). Several quantitative changes in PUFAs suggest their involvement in BD pathogenesis. Therefore, this study aimed to clarify the relationship between BD and PUFAs by conducting lipidomics covariating with the FADS gene variant (rs174550), which is associated with PUFA levels and BD susceptibility. The concentrations of 23 fatty acids were measured using plasma samples from the BD group (n = 535) and the control group (n = 107). Differences in each PUFA concentration ratio were compared between the two groups. Also, differences in each PUFA concentration ratio were compared for each genotype in rs174550. Our results showed that the BD group had significantly lower concentrations of linoleic acid (LA) (β = -0.36, p = 0.023) and arachidonic acid (AA) (β = -0.18, p = 0.013) than the control group. Concerning the effect of FADS on the PUFA concentration ratio, carriers of C-allele at rs174550 had significantly decreased γ-linolenic acid and AA concentration ratios. A previous GWAS reported that the presence of a C-allele at rs174550 increased the BD risk. This direction is consistent with the lipidomic results of the present study. In conclusion, both the FADS and BD were considered to regulate the AA concentration. Thus, as the FADS gene variant is crucial for conducting lipidomics of BD we believe that the allele frequency of FADS must be analyzed.
最近的全基因组关联研究（GWAS）已经确定了脂肪酸去饱和酶（FADS）基因，这些基因编码多不饱和脂肪酸（PUFA）去饱和过程中的关键酶，是双相障碍（BD）的易感基因。几种多不饱和脂肪酸的定量变化表明它们参与了 BD 的发病机制。因此，本研究旨在通过进行脂质组学分析，阐明 BD 与多不饱和脂肪酸之间的关系，并与与 PUFA 水平和 BD 易感性相关的 FADS 基因变异（rs174550）相关联。使用来自 BD 组（n=535）和对照组（n=107）的血浆样本测量了 23 种脂肪酸的浓度。比较了两组之间每种 PUFA 浓度比的差异。此外，还比较了 rs174550 中每种基因型的每种 PUFA 浓度比的差异。我们的研究结果表明，BD 组的亚油酸（LA）（β=-0.36，p=0.023）和花生四烯酸（AA）（β=-0.18，p=0.013）浓度明显低于对照组。关于 FADS 对 PUFA 浓度比的影响，rs174550 中 C 等位基因的携带者γ-亚麻酸和 AA 浓度比显著降低。之前的 GWAS 报道 rs174550 中 C 等位基因的存在增加了 BD 的风险。这个方向与本研究的脂质组学结果一致。综上所述，FADS 和 BD 都被认为可以调节 AA 浓度。因此，由于 FADS 基因变异对进行 BD 的脂质组学研究至关重要，我们认为必须分析 FADS 的等位基因频率。
