Genetic variant rs9939609 in<i>FTO</i>is associated with body composition and obesity risk in Korean females

Park, Hyeon-Gyo; Choi, Jeong-Hwa

doi:10.1136/bmjdrc-2023-003649

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…A meta-analysis performed by Zhao et al identified a strong association between FTO SNPs and obesity risk in the Chinese population (OR 1.30; 95% CI: 1.19-1.42, P < 0.0001) [22]. Park and Choi showed that FTO rs9939609 is associated with obesity risk in Korean women [23]. A study conducted by Perez-Luque et al on the Mexican population found that rs9939609, rs9930506, and rs1421085 are key to gaining weight after bariatric surgery [24].…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of Fat Mass and Obesity-Associated (FTO) Single Nucleotide Polymorphisms and Methylation in Breast Cancer

Hernández-Caballero,

Sierra-Ramírez,

De la Peña-Gutierrez

et al. 2024

Cureus

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Background Fat mass and obesity-associated (FTO) protein is an mRNA demethylase enzyme essential for active genome regulation. The FTO gene codes for a protein that is part of the methylosome complex and has a regulatory role in cancer development. Some studies have shown a relationship between FTO and cancer, where single nucleotide polymorphisms (SNPs) may have some impact on cancer risk. The present study aimed to evaluate the risk of FTO polymorphisms rs9939609, rs1477196, and rs9930506; analyze the methylation status of FTO promoters among Mexican women with breast cancer (BC); and investigate by in silico analysis the methylation status in the region near these polymorphisms. Methods A total of 157 BC patients and 137 healthy controls were genotyped for rs9939609, rs1477196, and rs9930506 FTO polymorphisms by TaqMan SNP Genotyping Assays. Promoter methylation was analyzed by sodium bisulfite and methylation-specific polymerase chain reaction (MSP) for 78 tissue samples. An in silico analysis using The Cancer Genome Atlas Program (TCGA) database was employed to investigate the methylation state in promoter and near polymorphism locations and its relation to survival. Results The AG genotype of FTO rs9930506 was associated with BC protection (P= 0.0025; adjusted OR, 0.27; 95% CI: 0.10-0.70). rs9939609 and rs1477196, according to the results of the present study, had no relation to BC. Promoter methylation status assays by MSP revealed no changes in methylation in BC or healthy tissues. Trying to know more about the methylation in promoters and near polymorphisms’ relation to survival, we performed an in silico analysis. Bioinformatics analysis showed a correlation between poor survival and methylation near polymorphisms but not with methylation in the promoter region. Conclusions The AG genotype rs9930506 has a protective function against BC. Whereas high methylation near polymorphisms was related to lower survival, the hypomethylated promoter region does not impact survival.

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Section: Discussionmentioning

confidence: 99%

Investigating the Role of Fat Mass and Obesity-Associated (FTO) Single Nucleotide Polymorphisms and Methylation in Breast Cancer

Hernández-Caballero,

Sierra-Ramírez,

De la Peña-Gutierrez

et al. 2024

Cureus

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“…An often studied SNP is rs9939609homozygous for this variant in adults has a 1.67-fold increased risk of obesity [107]. Park and Choi found this dependence, especially in women [108]. Studies demonstrate that FTO SNPs may also be associated with lean mass index (LMI) and sarcopenia [109].…”

Section: Genetic Susceptibility To Sarcopenic Obesitymentioning

confidence: 99%

Immunogenetic Aspects of Sarcopenic Obesity

Mazurkiewicz,

Czernikiewicz,

Grygiel-Górniak

2024

Genes

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Sarcopenic obesity (SO) is a combination of obesity and sarcopenia, with diagnostic criteria defined as impaired skeletal muscle function and altered body composition (e.g., increased fat mass and reduced muscle mass). The mechanism of SO is not yet perfectly understood; however, the pathogenesis includes aging and its complications, chronic inflammation, insulin resistance (IR), and hormonal changes. Genetic background is apparent in the pathogenesis of isolated obesity, which is most often polygenic and is characterized by the additive effect of various genetic factors. The genetic etiology has not been strictly established in SO. Still, many data confirm the existence of pathogenic gene variants, e.g., Fat Mass and Obesity Associated Gene (FTO), beta-2-adrenergic receptor (ADRB2) gene, melanocortin-4 receptor (MC4R) and others with obesity. The literature on the role of these genes is scarce, and their role has not yet been thoroughly established. On the other hand, the involvement of systemic inflammation due to increased adipose tissue in SO plays a significant role in its pathophysiology through the synthesis of various cytokines such as monocyte chemoattractant protein-1 (MCP-1), IL-1Ra, IL-15, adiponectin or CRP. The lack of anti-inflammatory cytokine (e.g., IL-15) can increase SO risk, but further studies are needed to evaluate the exact mechanisms of implications of various cytokines in SO individuals. This manuscript analyses various immunogenetic and non-genetic factors and summarizes the recent findings on immunogenetics potentially impacting SO development.

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Effects of the Interaction Between Oxidative Balance Score and Polygenic Risk Scores on Incidence of Metabolic Syndrome in Middle-Aged Korean Adults

Kim,

Shin

2024

Antioxidants

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Oxidative stress is implicated in insulin resistance, obesity, and metabolic syndromes (MetSs). However, the interplay between oxidative stress and genetic predisposition during the development of MetS remains unclear. In this study, we aimed to investigate the effects of the interaction between oxidative balance score (OBS) and polygenic risk score (PRS) on the incidence of MetS in middle-aged Korean adults. We analyzed data from 25,879 participants aged ≥40 years from the Health Examinees Cohort of the Korean Genome and Epidemiology Study. The OBS was calculated using 11 antioxidant and five pro-oxidant factors. A genome-wide association study and clumping analysis identified 16 independent single-nucleotide polymorphisms associated with MetS that were used to calculate individual PRSs. Multivariable Cox proportional hazard models adjusted for confounding variables were used to assess the impact of OBS and PRS on the incidence of MetS. During a mean follow-up period of 4.3 years, we recorded 3153 cases of MetS. In both men and women, the group with the lowest OBS and a high PRS had a 1.50-fold (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07–2.11) and 1.89-fold (HR 1.89, 95% CI 1.40–2.56) higher incidence, respectively, of MetS compared to those with the highest OBS and a low PRS. Among women with a high PRS, the HRs decreased significantly across OBS quintiles 1 through 5 (p for trend = 0.009). These findings suggest that managing the oxidative balance may be particularly crucial for individuals with a high genetic risk for MetS.

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Genetic variant rs9939609 inFTOis associated with body composition and obesity risk in Korean females

Cited by 3 publications

References 42 publications

Investigating the Role of Fat Mass and Obesity-Associated (FTO) Single Nucleotide Polymorphisms and Methylation in Breast Cancer

Investigating the Role of Fat Mass and Obesity-Associated (FTO) Single Nucleotide Polymorphisms and Methylation in Breast Cancer

Immunogenetic Aspects of Sarcopenic Obesity

Effects of the Interaction Between Oxidative Balance Score and Polygenic Risk Scores on Incidence of Metabolic Syndrome in Middle-Aged Korean Adults

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