FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men

Kamura, Yutaka; Iwata, Minoru; Maeda, Shiro; Shinmura, Satomi; Koshimizu, Yukiko; Honoki, Hisae; Fukuda, Kazuhito; Ishiki, Manabu; Usui, Isao; Fukushima, Yasuo; Takano, Atsuko; Kato, Hiromi; Murakami, Shihou; Higuchi, Kenichi; Kobashi, Chikaaki; Tobe, Kazuyuki

doi:10.1371/journal.pone.0165523

Cited by 31 publications

(20 citation statements)

References 56 publications

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“…A recent study by Kamura et al [25] suggested that the association between FTO variants and T2D is mediated through the lifetime maximum BMI at the time of or before diagnosis of T2D. Nevertheless, our lack of association with the T2D risk has also been reported in populations of similar genetic background to the Kuwaiti population [26, 27].…”

Section: Discussionmentioning

confidence: 54%

Association of FTO rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

et al. 2018

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Objective: To investigate the effect of the common fat mass and obesity-associated (FTO) gene polymorphism rs9939609 on body mass index (BMI) in one of the most obese populations worldwide. Subjects and Methods: Genotypic data for FTO rs9939609 were available for 1,034 unrelated Kuwaiti adults obtained from Kuwait’s Dasman Diabetes Institute and Kuwait University. The association between the FTO polymorphism with BMI as continuous and categorical (normal BMI [< 25] vs. overweight/obese [> 25]) variables was analyzed using both linear and logistic regression models, respectively, with the assumption of both dominant and additive genetic models performed using the SNPassoc package from R statistics. Results: The A allele was associated with increased BMI (β = 1.21; 95% CI = 0.16–2.26; p = 0.023). In concordance, the categorical BMI (normal vs. overweight/obese) also showed a significant association between the A allele and overweight/obesity (OR = 1.47; 95% CI = 1.01–2.12; p = 0.041). However, no association between the FTO variant was observed with cardiometabolic traits. Conclusion: We observed an association between the common FTO rs9939609 polymorphism and increased BMI (overweight/obesity) in Kuwaiti adults, which is consistent with previous research in other populations. Our findings encourage further investigation of genetic variants to elucidate the mechanisms involved in the development of obesity in such an obesogenic population.

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Section: Discussionmentioning

confidence: 54%

Association of FTO rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

et al. 2018

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“…Its association with T2D was also reported (22). The effects of FTO polymorphisms on T2D susceptibility may be mediated through their effect on increasing the lifetime maximum BMI before or at the time of diagnosis (23). However, in two metaanalysis on GDM, no associations between FTO polymorphisms (rs9939609, rs8050136, rs1421085, rs9939609, and rs8050136) and GDM risk were found (24,25).…”

Section: Discussionmentioning

confidence: 99%

Genetic Susceptibility to Gestational Diabetes Mellitus in a Chinese Population

et al. 2020

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Introduction: New genetic variants associated with susceptibility to obesity and metabolic diseases have been discovered in recent genome-wide association (GWA) studies. The aim of this study was to investigate the association of theses risk variants with gestational diabetes mellitus (GDM). Methods: We performed a case-control study including 964 unrelated pregnant women with GDM and 1,021 pregnant women with normal glucose tolerance (as controls). A total of 33 genetic variants confirmed by GWA studies for obesity and metabolic diseases were selected and measured. Results: We observed that FTO rs1121980 and KCNQ1 rs163182 conferred a decreased GDM risk in the dominant and additive model [additive model: OR (95% CI) = 0.79 (0.67-0.94), P = 0.007 for rs1121980; OR(95%CI) = 0.84 (0.73-0.96), P = 0.009 for rs163182], whereas MC4R rs12970134 and PROX1 rs340841 conferred an increased GDM risk in the dominant, recessive, and additive model [additive model: OR(95%CI) = 1.25 (1.07-1.46), P = 0.006 for rs12970134; OR(95%CI) = 1.22 (1.07-1.39), P = 0.002 for rs340841). With the increasing number of risk alleles of the four significant SNPs, GDM risk was significantly increased in a dose-dependent manner (P trend < 0.001). And the significant positive associations between the weighted genetic risk score and risk of GDM persisted. Further function annotation indicated that these four SNPs may fall on the functional elements of human pancreatic islets. The genotype-phenotype associations indicated that these SNPs may contribute to GDM by affecting the expression levels of their nearby or distant genes. Conclusion: Our study suggests that FTO rs1121980, KCNQ1 rs163182, MC4R rs12970134, and PROX1 rs340841 may be markers for susceptibility to GDM in a Chinese population.

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“…Also, we did not observe any possible haplotype associated with T2DM in the strong linkage disequilibrium region (block 1). While some other studies showed there were strong association between FTO variants and T2DM [10,[27][28][29][30][31]. The different ethnicities and race, cross-sectional design, and small sample size may lead to inconsistent results.…”

Section: Discussionmentioning

confidence: 96%

Association of FTO methylation level with incident type 2 diabetes mellitus: a nested case–control study within the Rural Chinese Cohort Study

Huang

Chen²,

Zhang

et al. 2020

Preprint

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Objectives This study aimed to investigate the association of FTO methylation level with type 2 diabetes mellitus (T2DM). Methods We conducted a nested case – control study for DNA methylation of FTO in Chinese pople identified from the Rural Chinese Cohort Study with a 6-year follow-up. Controls were matched to the cases on a 1:1 basis by age, sex, ethnicity, marital status, and residence. Unconditional multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for association with Tag-single nucleotide polymorphisms (SNPs) and cytosine guanine (CpG) locus. Haploview was used to analyze the association of possible haplotypes with T2DM. Generalized Multifactor Dimensionality Reduction was used to explore the potential interaction. Results We found a significant association for the CpG9 locus located in the promoter region of FTO with T2DM. With CpG9, the risk of T2DM was 1.84 (1.21–2.80) after adjusting for potential confounders. The Tag-SNPs (rs72803657, rs1558902, rs17817449, rs11076023) nor were possible haplotypes associated with T2DM in the strong linkage disequilibrium region. We found no significant interaction between obesity indexes, serum lipid levels and methylation levels. Conclusions Our study identified a CpG locus located in the promoter region of FTO that altered the T2DM risk independent of body mass index, but the variants of FTO were not significantly associated with T2DM. Our study might provide new insights into the pathways of FTO with T2DM and offer new opportunities for risk stratification and prevention of T2DM among rural Chinese population.

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FTO Gene Polymorphism Is Associated with Type 2 Diabetes through Its Effect on Increasing the Maximum BMI in Japanese Men

Cited by 31 publications

References 56 publications

Association of <b><i>FTO</i></b> rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

Association of <b><i>FTO</i></b> rs9939609 with Obesity in the Kuwaiti Population: A Public Health Concern?

Genetic Susceptibility to Gestational Diabetes Mellitus in a Chinese Population

Association of FTO methylation level with incident type 2 diabetes mellitus: a nested case–control study within the Rural Chinese Cohort Study

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