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A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

ABSTRACT: Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance (P=10-9). rs3757840 was also highly significantly associated with fasting glucose (P=8x10-7), but haplotype analysis revealed that this is explained by linkage disequilibrium (r2=0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g) increase in offspring birth weight (P=.002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

SUBMITTER: Weedon MN

PROVIDER: S-EPMC1698701 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

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A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

Weedon Michael N MN Clark Vanessa J VJ Qian Yudong Y Ben-Shlomo Yoav Y Timpson Nicholas N Ebrahim Shah S Lawlor Debbie A DA Pembrey Marcus E ME Ring Susan S Wilkin Terry J TJ Voss Linda D LD Jeffery Alison N AN Metcalf Brad B Ferrucci Luigi L Corsi Anna Maria AM Murray Anna A Melzer David D Knight Bridget B Shields Bev B Smith George Davey GD Hattersley Andrew T AT Di Rienzo Anna A Frayling Tim M TM

American journal of human genetics 20061006 6

Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explain ...[more]

PMID: 17186458

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Project description:BackgroundRamadan is a monthlong fast for healthy adolescents and adult Muslims. The quality of foods eaten and eating patterns in Ramadan may be different from other months of the year. Food intake of adolescents is a concern as energy and nutrient requirements are higher and needed to support the growth spurt of this stage. The objective of the present study was to describe the food patterns, dietary diversity and body weight changes among adolescents during Ramadan.MethodsA prospective cohort study design with four measurement points (baseline, midline, endline and post endline) was conducted among 366 adolescents in Junior High Schools. Food pattern was assessed with a food frequency questionnaire, a 24-h dietary recall was used to assess dietary diversity and body weight was measured using an electronic scale. A repeated measures ANOVA was used to compare changes in dietary diversity scores (DDS) and weight of pupils.ResultsHalf of the pupils (50.3%) were female and average age was 15.9 ± 1.8 years. Pupils fasted for an average of 28.3 ± 4.0 days and 14.3 ± 0.5 h a day (dawn to dusk) during Ramadan. The number and types of dishes taken at meal times differed substantially between Ramadan periods and outside Ramadan. Consumption of vitamin A-rich fruits, other fruits, and milk and milk products increased markedly during Ramadan. However, fasting came with a reduction in consumption of foods from roots and tubers, legumes and nuts, and dark green leafy vegetables while other food groups remained unchanged. Mean DDS increased significantly during Ramadan (F (2.933, 1070.573) = 7.152, p < 0.001) while mean daily meal frequency decreased (F (2.936, 1071.623) = 51.653, p < 0.001). There was significant body weight loss (-1.5 kg (95% CI: -1.1 kg to -1.6 kg)) among adolescents (F (2.656, 958.95) = 304.90, p < 0.001). Weight loss was short-lived; regained one month after Ramadan.ConclusionIn this prospective cohort study among schooling Ghanaian adolescents who fast during Ramadan, fasting was characterised by marked changes in usual food patterns, increased dietary diversity and significant body weight loss.

Dataset Information

A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

Publications

A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

Similar Datasets

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