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European lactase persistence genotype shows evidence of association with increase in body mass index.

ABSTRACT: The global prevalence of obesity has increased significantly in recent decades, mainly due to excess calorie intake and increasingly sedentary lifestyle. Here, we test the association between obesity measured by body mass index (BMI) and one of the best-known genetic variants showing strong selective pressure: the functional variant in the cis-regulatory element of the lactase gene. We tested this variant since it is presumed to provide nutritional advantage in specific physical and cultural environments. We genetically defined lactase persistence (LP) in 31 720 individuals from eight European population-based studies and one family study by genotyping or imputing the European LP variant (rs4988235). We performed a meta-analysis by pooling the beta-coefficient estimates of the relationship between rs4988235 and BMI from the nine studies and found that the carriers of the allele responsible for LP among Europeans showed higher BMI (P = 7.9 x 10(-5)). Since this locus has been shown to be prone to population stratification, we paid special attention to reveal any population substructure which might be responsible for the association signal. The best evidence of exclusion of stratification came from the Dutch family sample which is robust for stratification. In this study, we highlight issues in model selection in the genome-wide association studies and problems in imputation of these special genomic regions.

SUBMITTER: Kettunen J

PROVIDER: S-EPMC2830824 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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European lactase persistence genotype shows evidence of association with increase in body mass index.

Kettunen Johannes J Silander Kaisa K Saarela Olli O Amin Najaf N Müller Martina M Timpson Nicholas N Surakka Ida I Ripatti Samuli S Laitinen Jaana J Hartikainen Anna-Liisa AL Pouta Anneli A Lahermo Päivi P Anttila Verneri V Männistö Satu S Jula Antti A Virtamo Jarmo J Salomaa Veikko V Lehtimäki Terho T Raitakari Olli O Gieger Christian C Wichmann Erich H EH Van Duijn Cornelia M CM Smith George Davey GD McCarthy Mark I MI Järvelin Marjo-Riitta MR Perola Markus M Peltonen Leena L

Human molecular genetics 20091216 6

The global prevalence of obesity has increased significantly in recent decades, mainly due to excess calorie intake and increasingly sedentary lifestyle. Here, we test the association between obesity measured by body mass index (BMI) and one of the best-known genetic variants showing strong selective pressure: the functional variant in the cis-regulatory element of the lactase gene. We tested this variant since it is presumed to provide nutritional advantage in specific physical and cultural env ...[more]

PMID: 20015952

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Project description:Abstract Objectives Lactase persistence (LP), a heritable trait in which lactose can be digested throughout adulthood, is often used to predict dairy intake. However, it is currently unknown how LP relates to daily lactose consumption in healthy US adults. The objective of the study was to estimate lactose from foods reported in the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) and to compare lactose and total dairy consumption in relation to LP genotypes. Methods ASA24 dietary data were collected from healthy Caucasians and Hispanics (n = 215) genotyped for the lactase persistence SNP ID: rs4988235. ASA24 outputs servings of dairy but not the nutrient lactose. Lactose was estimated by matching ASA24-reported foods to foods in the Nutrition Coordinating Center Food and Nutrient Database, which outputs lactose. Analysis of covariance was used to identify whether genotype influenced lactose and total dairy consumption with total energy intake and weight as covariates. Pairwise testing was conducted on the adjusted means using the Tukey adjustment to correct for multiple testing. Results Median lactose consumption for subjects with the AA genotype (homozygous LP) was 12.08 g (min: 0.91 g, max: 81.85 g), 10.05 g (min: 0.46 g, max: 45.82) for subjects with the AG genotype (heterozygous LP), and 8.97 g (min: 0.47, max: 38.96 g) for subjects with the GG genotype (homozygous lactase non-persistent). AA subjects consumed more lactose than GG subjects (P = 0.024). When stratifying by sex, there were no significant differences among genotypes in women, although GG women consumed the least amount of lactose compared to AA and AG women. AA men consumed more lactose than AG (P = 0.028) and GG men (P = 0.032). Subjects with the AA genotype consumed the most, and GG subjects the least amount of dairy. However, there were no significant differences in total dairy consumption among genotypes. Conclusions The median amount of lactose consumed daily by healthy adults is 9–12 g/day, with higher consumption by those with an LP genotype. Total dairy intake was not significantly influenced by genotype, highlighting the value in specifically estimating lactose consumption. Maximal lactose intake by lactase non-persisters exceeding 15 g/day suggests alternate routes of lactose catabolism. Funding Sources The California Dairy Research Foundation and the USDA-ARS.

Dataset Information

European lactase persistence genotype shows evidence of association with increase in body mass index.

Publications

European lactase persistence genotype shows evidence of association with increase in body mass index.

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