Ramathibodi Hospital, Bangkok, Thailand.
PeerJ. 2022 Jun 21;10:e13612. doi: 10.7717/peerj.13612. eCollection 2022.
Genome-wide association studies have identified the alpha-ketoglutarate dependent dioxygenase gene (FTO) as the first susceptibility gene of obesity. In the present study, we utilized targeted metabolomics in an attempt to further elucidate mechanisms underlying the action of the FTO gene.
This study was part of a health survey of employees of the Electricity Generating Authority of Thailand ( = 79, 10 female and 69 male). Targeted metabolomics was performed by liquid chromatography-mass spectrometry using Biocrates AbsoluteIDQ-p180 kit. Genotyping of FTO rs9939609 was performed by real-time PCR (TaqMan™ MGB probes).
Using OPLS-DA variable importance in projection (VIP), tryptophan was found to be among the metabolites with the 10 highest VIP scores. Pearson's correlation analysis showed that kynurenine and tryptophan were positively correlated only in subjects with the rs9939609 A allele ( = 32, = 0.56, < 0.001) and the correlation coefficients were significantly higher in subjects having the A allele than in those without the A allele ( < 0.05). Moreover, the kynurenine/tryptophan ratio was significantly associated with the presence of the A allele, independently of body mass index and sex.
The FTO gene is likely to influences the conversion of tryptophan to kynurenine.
全基因组关联研究已经确定了α-酮戊二酸依赖性双加氧酶基因（FTO）是肥胖的第一个易感基因。在本研究中，我们利用靶向代谢组学试图进一步阐明 FTO 基因作用的机制。
该研究是泰国发电局（Egat）员工健康调查的一部分（=79 人，10 名女性，69 名男性）。通过液相色谱-质谱联用技术，使用 Biocrates AbsoluteIDQ-p180 试剂盒进行靶向代谢组学分析。FTO rs9939609 的基因分型通过实时 PCR（TaqMan™ MGB 探针）进行。
利用 OPLS-DA 变量重要性投影（VIP），发现色氨酸是代谢物中 VIP 得分最高的 10 种之一。皮尔逊相关分析表明，在携带 rs9939609 A 等位基因的个体中，犬尿酸和色氨酸呈正相关（=32，=0.56，<0.001），并且 A 等位基因携带者的相关系数明显高于无 A 等位基因携带者（<0.05）。此外，犬尿酸/色氨酸比值与 A 等位基因的存在显著相关，与体重指数和性别无关。
FTO 基因可能影响色氨酸向犬尿酸的转化。
