Abstract
Association studies have implicated single nucleotide polymorphisms (SNPs), particularly rs1421085, from the fat mass and obesity-associated (FTO) gene with body composition phenotypes, obesity, dietary intake, and physical activity in European, East Asian, and African populations. However, the impact of the rs1421085 variant has not been sufficiently tested in ethnic populations (such as Arabs) with high levels of obesity. Further, there is a lack of studies identifying biomarkers that interact with FTO. Therefore, we investigated the association of rs1421085 with obesity and body composition traits and metabolic biomarkers in Arab population. We genotyped rs1421085 SNP in 278 Arab individuals, where multiple biomarkers relating to obesity, inflammation, and other metabolic pathways were quantified. We performed genetic association tests under additive mode of inheritance using linear regression models and found association of rs1421085_C allele with higher levels of body weight, soft lean mass (SLM), and total body water. Examination (using linear regression models under dominant mode of inheritance) of correlation among biomarkers and interaction with genotypes at the variant revealed that measures of these three body composition traits were found mediated by interaction between carrier genotypes (TC+CC) and measures of ghrelin, ApoA1, and ApoB48. Lean body mass (LBM), to which SLM contributes, is an important determinant of physical strength and is a focal point in studies on sarcopenia. Low LBM is known to be associated with higher risk of cardiometabolic disorders. Thus, the finding on the FTO variant as a genetic determinant of SLM via interaction with ghrelin, ApoA1, and ApoB48 is important.
Highlights
The fat mass and obesity-associated (FTO) gene is a wellestablished obesity-susceptibility locus
We showed that the FTO variant, rs1421085, was associated with increased body weight, Total body water (TBW), and soft lean mass (SLM) in a cohort of Kuwaiti Arab subjects
Associations at borderline P-values were observed with lower levels of C-peptide; the inflammatory cytokines, IL-5, TNFa, and IFNg and the inflammatory chemokine, eotaxin. These observations corroborate the varied associations made by global genome-wide association studies (GWAS) between rs1421085 and various physiological processes, including early onset extreme obesity (Wheeler et al, 2013), body mass index (BMI) abnormalities in childhood (Felix et al, 2016), chronotype measurement (Jones et al, 2019), percentage body fat (Hubel et al, 2019), lean body mass, type 2 diabetes (Suzuki et al, 2019), energy intake (Tanaka et al, 2013), and hand grip strength (Tikkanen et al, 2018), that were identified in various ethnic groups
Summary
The fat mass and obesity-associated (FTO) gene is a wellestablished obesity-susceptibility locus. Association of FTO variants with type 2 diabetes mellitus (T2DM), independent of body mass index (BMI), has been demonstrated in East and South Asians (Li et al, 2012) and Scandinavians (Hertel et al, 2011). The most notable genetic variants from FTO associated with obesity and body composition traits are a cluster of at least 20 common SNPs from its first intron (Loos and Yeo, 2014). Obesity has reached epidemic proportions, and understanding its genetic basis will help mitigate obesity-associated illness. In this context, there is an urgent need to decipher the causal mechanism for the role of FTO noncoding variants in the aetiology of obesity and its related disorders (Wu and Arora, 2016)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
