INTRODUCTION: TMEM18 has been indicated by genome-wide association studies as a key gene linked to obesity, yet its exact function and connections with major metabolic networks are unknown. OBJECTIVES: The current study is aimed to determine whether the TMEM18 rs7561317 polymorphism linked with anthropometric indicators of obesity is accompanied with alterations in serum metabolites. METHODS: This was a case-control study in which a total of 542 participants (Pakistani nationals) were involved including overweight or obese cases and those having normal body mass index (BMI). All participants provided blood samples which were utilized to extract serum and genomic DNA. The genomic DNA of all participants was genotyped for the TMEM18 rs7561317 variant while their serum samples were subjected to untargeted gas chromatography-mass spectrometry based metabolomics. RESULTS: A total of 42 putatively annotated metabolites were selected for further statistical analyses. Analyses revealed that the TMEM18 gene variant (rs7561317) exhibited statistically significant association with five metabolites namely urea, eicosane, geraniol, pentadecanoic acid and porphine as well as with BMI, percent body fat, waist circumference and weight. The G allele of this variant appears to increase the risk of developing overweight or obesity and may be associated with metabolite alterations. CONCLUSION: The findings highlight the role of metabolite alterations in the manifestation of obese phenotype among individuals carrying the GG genotype of the TMEM18 rs7561317 variant.
Farooq et al. (2026) studied this question.