Search resultsDeterminants of HbA1c in nondiabetic Dutch adults: Genetic loci and clinical and lifestyle parameters, and their interactions in the lifelines cohort study
Title
Determinants of HbA1c in nondiabetic Dutch adults: Genetic loci and clinical and lifestyle parameters, and their interactions in the lifelines cohort study
Publication type
Journal Article
Year of Publication
2013
Authors
Journal
Journal of Internal Medicine
Volume
273
Issue
3
Pagination
283 - 293
Date published
2013
ISBN
09546820 (ISSN)
Keywords
Adult, age, alcohol consumption, Alcohol Drinking, article, body mass, cohort analysis, Cohort Studies, diabetes mellitus, erythrocyte index, Erythrocyte Indices, European Continental Ancestry Group, Female, gender, gene locus, Genetic Loci, Genetic risk score, genome, Genome-Wide Association Study, genotype, glucose, glucose blood level, HbA1c, hematological parameters, Hemoglobin A, Glycosylated, hemoglobin A1c, human, Humans, Life Style, lifestyle, male, Middle Aged, Netherlands, Nondiabetic, Polymorphism, Single Nucleotide, population research, priority journal, quality control, questionnaire, Replication, risk assessment, single nucleotide polymorphism, smoking, SNP, waist circumference
Abstract
Objectives: Glycated haemoglobin (HbA1c) is associated with cardiovascular disease risk in individuals without diabetes, and its use has been recommended for diagnosing diabetes. Therefore, it is important to gain further understanding of the determinants of HbA1c. The aim of this study was to investigate the effects of genetic loci and clinical and lifestyle parameters, and their interactions, on HbA1c in nondiabetic adults. Design: Population-based cohort study. Setting: Three northern provinces of the Netherlands. Subjects: A total of 2921 nondiabetic adults participating in the population-based LifeLines Cohort Study. Measurements: Body mass index (BMI), waist circumference, HbA1c, fasting plasma glucose (FPG) and erythrocyte indices were measured. Data on current smoking and alcohol consumption were collected through questionnaires. Genome-wide genotyping was performed, and 12 previously identified single-nucleotide polymorphisms (SNPs) were selected for replication and categorized as 'glycaemic' and 'nonglycaemic' SNPs according to their presumed mechanism(s) of action on HbA1c. Genetic risk scores (GRSs) were calculated as the sum of the weighted effect of HbA1c-increasing alleles. Results: Age, gender, BMI, FPG, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, current smoking and alcohol consumption were independent predictors of HbA1c, together explaining 26.2% of the variance in HbA1c, with FPG contributing 10.9%. We replicated three of the previously identified SNPs and the GRSs were also found to be independently associated with HbA1c. We found a smaller effect of the 'nonglycaemic GRS' in females compared with males and an attenuation of the effect of the GRS of all 12 SNPs with increasing BMI. Conclusions: Our results suggest that a substantial portion of HbA1c is determined by nonglycaemic factors. This should be taken into account when considering the use of HbA1c as a diagnostic test for diabetes.