Association of DNA methylation with age, gender, and smoking in an Arab population.

BACKGROUND: Modification of DNA by methylation of cytosines at CpG dinucleotides is a widespread phenomenon that leads to changes in gene expression, thereby influencing and regulating many biological processes. Recent technical advances in the genome-wide determination of single-base DNA-methylation enabled epigenome-wide association studies (EWASs). Early EWASs established robust associations between age and gender with the degree of CpG methylation at specific sites. Other studies uncovered associations with cigarette smoking. However, so far these studies were mainly conducted in Caucasians, raising the question of whether these findings can also be extrapolated to other populations. RESULTS: Here, we present an EWAS with age, gender, and smoking status in a family study of 123 individuals of Arab descent. We determined DNA methylation at over 450,000 CpG sites using the Illumina Infinium HumanMethylation450 BeadChip, applied state-of-the-art data processing protocols, including correction for blood cell type heterogeneity and hidden confounders, and eliminated probes containing SNPs at the targeted CpG site using 40× whole-genome sequencing data. Using this approach, we could replicate the leading published EWAS associations with age, gender and smoking, and recovered hallmarks of gender-specific epigenetic changes. Interestingly, we could even replicate the recently reported precise prediction of chronological age based on the methylation of only a few selected CpG sites. CONCLUSION: Our study supports the view that when applied with state-of-the art protocols to account for all potential confounders, DNA methylation arrays represent powerful tools for EWAS with more complex phenotypes that can also be successfully applied to non-Caucasian populations

Elevated HbA1c levels in individuals not diagnosed with type 2 diabetes in Qatar: A pilot study.

Background: The prevalence of type 2 diabetes (T2D) in Qatar and the Middle East is one of the highest in the world. It is estimated that about one quarter of the individuals with T2D are undiagnosed. Elevated HbA1c levels are an indicator of T2D or a pre-diabetic state. In this study we set out to examine which factors, such as anthropometric and socio-demographic risk factors, are associated with elevated HbA1c levels in a population without T2D. Methods: We examined 191 subjects with no record of T2D. Anthropometrics and HbA1c were measured. Socio-demographic (age, gender, ethnicity and educational level) and health information were assessed through questionnaires. Elevated HbA1c levels were defined as >6.0% (>42 mmol/mol). Individual risk factors were examined in relationship to having elevated HbA1c levels using logistic regression. Results: Thirty-eight (20%) study participants had elevated HbA1c levels. Participants from South Asian and Filipino descent were more likely to present with elevated HbA1c levels than Arab participants (adjusted odds ratios (OR): 13.30 (95% confidence interval (CI): 4.24, 41.79), p <0.001 for South Asian and 4.54 (95% CI: 1.04, 19.83), p= 0.04 for Filipinos). A body mass index of above 30 kg/m2 was associated with elevated HbA1c levels (adjusted OR: 2.90 (95% CI: 1.29, 6.51), p= 0.01). Neither gender nor educational level was associated with elevated HbA1c levels. Conclusions: Elevated HbA1c levels in individuals not diagnosed with diabetes were most frequently found in the South Asian and Filipino immigrant population. Special attention should therefore be given to the early identification of T2D in these subjects

1,5-anhydroglucitol in saliva is a noninvasive marker of short-term glycemic control.

Context: In most ethnicities at least a quarter of all cases with diabetes is assumed to be undiagnosed. Screening for diabetes using saliva has been suggested as an effective approach to identify affected individuals. Objective: The objective of the study was to identify a noninvasive metabolic marker of type 2 diabetes in saliva. Design and Setting: In a case-control study of type 2 diabetes, we used a clinical metabolomics discovery study to screen for diabetes-relevant metabolic readouts in saliva, using blood and urine as a reference. With a combination of three metabolomics platforms based on nontargeted mass spectrometry, we examined 2178 metabolites in saliva, blood plasma, and urine samples from 188 subjects with type 2 diabetes and 181 controls of Arab and Asian ethnicities. Results: We found a strong association of type 2 diabetes with 1,5-anhydroglucitol (1,5-AG) in saliva (P = 3.6 x 10(-13)). Levels of 1,5-AG in saliva highly correlated with 1,5-AG levels in blood and inversely correlated with blood glucose and glycosylated hemoglobin levels. These findings were robust across three different non-Caucasian ethnicities (Arabs, South Asians, and Filipinos), irrespective of body mass index, age, and gender. Conclusions: Clinical studies have already established 1,5-AG in blood as a reliable marker of short-term glycemic control. Our study suggests that 1,5-AG in saliva can be used in national screening programs for undiagnosed diabetes, which are of particular interest for Middle Eastern countries with young populations and exceptionally high diabetes rates