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      Association of the European Lactase Persistence Variant (LCT-13910 C>T Polymorphism) with Obesity in the Canary Islands

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          Abstract

          Background

          European lactose tolerance genotype (LCT -13910 C>T, rs4988234) has been positively associated to body mass indexes (BMI) in a meta-analysis of 31,720 individuals of northern and central European descent. A strong association of lactase persistence (LP) with BMI and obesity has also been traced in a Spanish Mediterranean population. The aim of this study was to analyze a potential association of LP compared to lactase non-persistence (LNP) with BMI in inhabitants of the Canary Islands of Spain using Mendelian randomization.

          Methods

          A representative, randomly sampled population of adults belonging to the Canary Islands Nutrition Survey (ENCA) in Spain, aged 18–75 years (n = 551), was genotyped for the LCT – 13910 C>T polymorphism. Milk consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured. WHO classification of BMI was used.

          Results

          LP individuals were significantly more obese than LNP subjects ( χ 2  = 10.59; p<0.005). LP showed in a multivariate linear regression analysis showed a positive association of LP with BMI compared to LNP, ( β = 0.96; 95% CI: 0.08–1.85, p = 0.033). In a multinomial logistic regression analysis normal range weight LP subjects showed an odds ratio for obesity of 2.41; 95%CI 1.39–418, ( p = 0.002) compared to LNP.

          Conclusions

          The T-13910 of the allele LCT-13910 C>T polymorphism is positively associated with BMI. LP increases significantly the risk to develop obesity in the studied population. The LCT-13910 C>T polymorphism stands proxy for the lifetime exposure pattern, milk intake, that may increase susceptibility to obesity and to obesity related pathologies.

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          Most cited references27

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          'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?

          Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization-the random assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian randomization and are described. The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study, that polymorphisms may have several phenotypic effects associated with disease, the lack of suitable polymorphisms for studying modifiable exposures of interest, and canalization-the buffering of the effects of genetic variation during development. Nevertheless, Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.
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            Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations.

            We analyzed genome-wide association data from 1,380 Europeans with early-onset and morbid adult obesity and 1,416 age-matched normal-weight controls. Thirty-eight markers showing strong association were further evaluated in 14,186 European subjects. In addition to FTO and MC4R, we detected significant association of obesity with three new risk loci in NPC1 (endosomal/lysosomal Niemann-Pick C1 gene, P = 2.9 x 10(-7)), near MAF (encoding the transcription factor c-MAF, P = 3.8 x 10(-13)) and near PTER (phosphotriesterase-related gene, P = 2.1 x 10(-7)).
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              Milk and dairy consumption and incidence of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies.

              The consumption of dairy products may influence the risk of cardiovascular disease (CVD) and total mortality, but conflicting findings have been reported. The objective was to examine the associations of milk, total dairy products, and high- and low-fat dairy intakes with the risk of CVD [including coronary heart disease (CHD) and stroke] and total mortality. PubMed, EMBASE, and SCOPUS were searched for articles published up to February 2010. Of > 5000 titles evaluated, 17 met the inclusion criteria, all of which were original prospective cohort studies. Random-effects meta-analyses were performed with summarized dose-response data. Milk as the main dairy product was pooled in these analyses. In 17 prospective studies, there were 2283 CVD, 4391 CHD, 15,554 stroke, and 23,949 mortality cases. A modest inverse association was found between milk intake and risk of overall CVD [4 studies; relative risk (RR): 0.94 per 200 mL/d; 95% CI: 0.89, 0.99]. Milk intake was not associated with risk of CHD (6 studies; RR: 1.00; 95% CI: 0.96, 1.04), stroke (6 studies; RR: 0.87; 95% CI: 0.72, 1.05), or total mortality (8 studies; RR per 200 mL/d: 0.99; 95% CI: 0.95, 1.03). Limited studies of the association of total dairy products and of total high-fat and total low-fat dairy products (per 200 g/d) with CHD showed no significant associations. This dose-response meta-analysis of prospective studies indicates that milk intake is not associated with total mortality but may be inversely associated with overall CVD risk; however, these findings are based on limited numbers.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                24 August 2012
                : 7
                : 8
                : e43978
                Affiliations
                [1 ]Family Medicine Research Centre, School of Health and Medical Sciences, Örebro University, Örebro, Sweden
                [2 ]Preventive Medicine Service, Canary Health Service, Department of Clinical Sciences, Faculty of Health Sciences, University of Las Palmas de Gran Canaria, Canary Islands, Spain
                University of Utah, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: RA EEA-L LS-M. Performed the experiments: RA EEA-L LS-M. Analyzed the data: RA EEA-L. Contributed reagents/materials/analysis tools: RA EEA-L LS-M. Wrote the paper: RA. Read and approved the final manuscript: RA EEA-L LS-M.

                Article
                PONE-D-12-07298
                10.1371/journal.pone.0043978
                3427248
                22937140
                8b7a92a7-a20e-4e4e-b873-c1e06101103d
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 March 2012
                : 27 July 2012
                Page count
                Pages: 6
                Funding
                This project has been funded by the Spanish Canarian Health Service and Örebro County, Sweden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Computational Biology
                Genomics
                Genome Analysis Tools
                Genetic Screens
                Population Genetics
                Genetic Polymorphism
                Evolutionary Biology
                Population Genetics
                Genetic Polymorphism
                Genetics
                Human Genetics
                Genetic Association Studies
                Genetic Screens
                Genetics of Disease
                Medicine
                Epidemiology
                Genetic Epidemiology
                Nutrition
                Obesity
                Public Health

                Uncategorized
                Uncategorized

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