Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes

Ligthart, Symen; Steenaard, Rebecca V; Peters, Marjolein J.; Meurs, Joyce B. J. van; Sijbrands, Eric J.G.; Uitterlinden, André G.; Bonder, Marc Jan; Hofman, Albert; Franco, Oscar H.; Dehghan, Abbas

doi:10.1007/s00125-016-3872-0

Cited by 46 publications

(37 citation statements)

References 32 publications

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“…Interestingly, genes associated with “insulin receptor binding” and “negative regulation of glucose import” were enriched within the dataset, suggesting that smoking-induced diabetes susceptibility may arise from aberrant methylation of DNA [38]. In support of this theory, a recent paper found that cigarette smoking is associated with altered methylation patterns in several previously identified diabetes-related genes [39]…”

Section: Molecular Mechanisms Underlying the Development Of Altered Gmentioning

confidence: 97%

Smoking and the risk of type 2 diabetes

Maddatu

Anderson-Baucum

Evans‐Molina

2017

Translational Research

278

168

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Despite accumulating evidence demonstrating strong epidemiological and mechanistic associations between cigarette smoking, hyperglycemia, and the development of type 2 diabetes, tobacco abuse has not been uniformly recognized as a modifiable risk factor in diabetes prevention or screening strategies. In this review, we highlight population-based studies that have linked cigarette smoking with an increased risk of type 2 diabetes and summarize clinical and preclinical studies offering insight into mechanisms through which cigarette smoking and nicotine exposure impact body composition, insulin sensitivity, and pancreatic β cell function. Key questions for future studies are identified and strategies for smoking cessation as a means to decrease diabetes risk are discussed.

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Section: Molecular Mechanisms Underlying the Development Of Altered Gmentioning

confidence: 97%

Smoking and the risk of type 2 diabetes

Maddatu

Anderson-Baucum

Evans‐Molina

2017

Translational Research

278

168

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“…Moreover, tobacco smoking has been found to be associated with polymorphisms in the KCNQ1 gene, which is implicated in hypomethylation of cg26963277 (KCNQ1), a biological process relating D r a f t to lower fasting insulin levels (Ligthart et al 2016).…”

Section: R a F Tmentioning

confidence: 99%

Interactions between genetic polymorphisms of glucose metabolizing genes and smoking and alcohol consumption in the risk of type 2 diabetes mellitus

Gao

Ren

Wang

et al. 2017

Appl. Physiol. Nutr. Metab.

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The impact of gene-environment interaction on diabetes remains largely unknown. We aimed to investigate if interaction between glucose metabolizing genes and lifestyle factors is associated with type 2 diabetes mellitus (T2DM). Interactions between genotypes of 4 glucose metabolizing genes (MTNR1B, KCNQ1, KLF14, and GCKR) and lifestyle factors were estimated in 722 T2DM patients and 759 controls, using multiple logistic regression. No significant associations with T2DM were detected for the single nucleotide polymorphisms of MTNR1B, KLF14 and GCKR. However, rs151290 (KCNQ1) polymorphisms were found to be associated with risk of T2DM. Compared with AA, the odds ratios (ORs) of AC or CC genotypes for developing T2DM were 1.545 (P = 0.0489) and 1.603 (P = 0.0383), respectively. In stratified analyses, the associations were stronger in smokers with CC than smokers with AA (OR = 3.668, P = 0.013); drinkers with AC (OR = 5.518, P = 0.036), CC (OR = 8.691, P = 0.0095), and AC+CC (OR = 6.764, P = 0.016) than drinkers with AA. Compared with nondrinkers with AA, drinkers who carry AC and CC had 12.072-fold (P = 0.0007) and 8.147-fold (P = 0.0052) higher risk of developing T2DM. In conclusions, rs151290 (KCNQ1) polymorphisms are associated with increased risk of T2DM, alone and especially in interaction with smoking and alcohol.

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“…Smoking is a well-known risk factor for the development of several diseases [13,14]. Therefore, studies that investigate smoking and its effect on mortality and morbidity rely on accurate assessments of smoking exposure.…”

Section: Introductionmentioning

confidence: 99%

Validated inference of smoking habits from blood with a finite DNA methylation marker set

et al. 2019

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Inferring a person's smoking habit and history from blood is relevant for complementing or replacing self-reports in epidemiological and public health research, and for forensic applications. However, a finite DNA methylation marker set and a validated statistical model based on a large dataset are not yet available. Employing 14 epigenome-wide association studies for marker discovery, and using data from six population-based cohorts (N = 3764) for model building, we identified 13 CpGs most suitable for inferring smoking versus non-smoking status from blood with a cumulative Area Under the Curve (AUC) of 0.901. Internal fivefold cross-validation yielded an average AUC of 0.897 ± 0.137, while external model validation in an independent population-based cohort (N = 1608) achieved an AUC of 0.911. These 13 CpGs also provided accurate inference of current (average AUC crossvalidation 0.925 ± 0.021, AUC externalvalidation 0.914), former (0.766 ± 0.023, 0.699) and never smoking (0.830 ± 0.019, 0.781) status, allowed inferring pack-years in current smokers (10 pack-years 0.800 ± 0.068, 0.796; 15 pack-years 0.767 ± 0.102, 0.752) and inferring smoking cessation time in former smokers (5 years 0.774 ± 0.024, 0.760; 10 years 0.766 ± 0.033, 0.764; 15 years 0.767 ± 0.020, 0.754). Model application to children revealed highly accurate inference of the true non-smoking status (6 years of age: accuracy 0.994, N = 355; 10 years: 0.994, N = 309), suggesting prenatal and passive smoking exposure having no impact on model applications in adults. The finite set of DNA methylation markers allow accurate inference of smoking habit, with comparable accuracy as plasma cotinine use, and smoking history from blood, which we envision becoming useful in epidemiology and public health research, and in medical and forensic applications.

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Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes

Cited by 46 publications

References 32 publications

Smoking and the risk of type 2 diabetes

Smoking and the risk of type 2 diabetes

Interactions between genetic polymorphisms of glucose metabolizing genes and smoking and alcohol consumption in the risk of type 2 diabetes mellitus

Validated inference of smoking habits from blood with a finite DNA methylation marker set

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