Genotypes of HLA, TCF7L2, and FTO as potential modifiers of the association between sweetened beverage consumption and risk of LADA and type 2 diabetes

Löfvenborg, Josefin E.; Ahlqvist, Emma; Alfredsson, Lars; Andersson, Tomas; Dorkhan, Mozhgan; Groop, Leif; Tuomi, Tiinamaija; Wolk, Alicja; Carlsson, Sofia

doi:10.1007/s00394-019-01893-x

Cited by 12 publications

(24 citation statements)

References 43 publications

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“…It should also be noted that the analyses of PA by genotype were hampered by relatively low numbers and overlapping CIs. Still, these findings fit with previous observations that high consumption of sweetened beverages only increases the risk of LADA in individuals without HLA risk genotypes ( 37 ). This would suggest that the influence of environmental factors in the etiology of LADA, and thus opportunities for lifestyle interventions, are larger in individuals without genetic susceptibility to diabetes.…”

Section: Discussionsupporting

confidence: 92%

Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

Hjort

Ahlqvist

Andersson

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

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Purpose Physical activity (PA) has been linked to a reduced risk of type 2 diabetes by reducing weight and improving insulin sensitivity. We investigated if PA is associated with a lower incidence of latent autoimmune diabetes in adults (LADA) and whether the association is modified by genotypes of HLA, TCF7L2-rs7903146, or FTO-rs9939609. Methods We combined data from a Swedish case-control study and a Norwegian prospective study including 621 incident cases of LADA and 3596 cases of type 2 diabetes. We estimated adjusted pooled relative risks (RR) and 95% confidence intervals (CI) of diabetes in relation to high (≥30 minutes of moderate activity three times/week) self-reported leisure time PA, compared to sedentariness. Results High PA was associated with a reduced risk of LADA (RR 0.61; CI 0.43-0.86), which was attenuated after adjustment for BMI (RR 0.90; CI 0.63-1.29). The reduced risk only applied to non-carriers of HLA-DQB1 and -DRB1 (RR 0.49, CI 0.33-0.72), TCF7L2 (RR 0.62, CI 0.45-0.87) and FTO (RR 0.51, CI 0.32-0.79) risk genotypes. Adjustment for BMI attenuated but did not eliminate these associations. For type 2 diabetes, there was an inverse association with PA (RR 0.49, CI 0.42-0.56), irrespective of genotype. Main Conclusions Our findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility.

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Section: Discussionsupporting

confidence: 92%

Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

Hjort

Ahlqvist

Andersson

et al. 2020

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…They show that the protective effect of whole-grain intake was lost in subjects who carried the T allele of rs7903146 in TCF7L2 [ 31 ]. Recently, in a Swedish case-control study conducted in a European population investigate whether the association between sweetened beverages and T2D is modified by TCF7L2 but there were no indications of synergistic effects [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

The Association between Fasting Glucose and Sugar Sweetened Beverages Intake Is Greater in Latin Americans with a High Polygenic Risk Score for Type 2 Diabetes Mellitus

et al. 2021

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Chile has the highest per capita intake of sugar-sweetened beverages (SSB) world-wide. However, it is unknown whether the effects from this highly industrialized food will mimic those reported in industrialized countries or whether they will be modified by local lifestyle or population genetics. Our goal was to evaluate the association between SSB intake and fasting glucose in the Chilean population. We calculated a weighted genetic risk score (GRSw) based on 16 T2D risk SNPs in 2828 non-diabetic participants of the MAUCO cohort. SSB intake was categorized in four levels using a food frequency questionnaire. Log-fasting glucose was regressed on SSB and GRSw tertiles while accounting for socio-demography, lifestyle, obesity, and Amerindian ancestry. Fasting glucose increased systematically per unit of GRSw (β = 0.02 ± 0.006, p = 0.00002) and by SSB intake (β[cat4] = 0.04 ± 0.009, p = 0.0001), showing a significant interaction, where the strongest effect was observed in the highest GRSw-tertile and in the highest SSB consumption category (β = 0.05 ± 0.02, p = 0.02). SNP-wise, SSB interacted with additive effects of rs7903146 (TCF7L2) (β = 0.05 ± 0.01, p = 0.002) and with the G/G genotype of rs10830963 (MTNRB1B) (β = 0.19 ± 0.05, p = 0.001). Conclusions: The association between SSB intake and fasting glucose in the Chilean population without diabetes is modified by T2D genetic susceptibility.

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“…Second, the association between CpG and T2DM might be influenced by other unmeasured confounding factors because some lifestyle factors have been found to influence the association between FTO with T2DM [7,[37][38][39][40]. In addition, we lacked serum transcription data, which needs further study.…”

Section: Discussionmentioning

confidence: 99%

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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Genotypes of HLA, TCF7L2, and FTO as potential modifiers of the association between sweetened beverage consumption and risk of LADA and type 2 diabetes

Cited by 12 publications

References 43 publications

Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

The Association between Fasting Glucose and Sugar Sweetened Beverages Intake Is Greater in Latin Americans with a High Polygenic Risk Score for Type 2 Diabetes Mellitus

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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