Document Detail


Genetic modifiers of nutritional status in cystic fibrosis.
MedLine Citation:
PMID:  23134884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Improved nutrition early in life is associated with better pulmonary function for patients with cystic fibrosis (CF). However, nutritional status is poorly correlated with the CFTR genotype.
OBJECTIVE: We investigated the extent to which modifier genes influence nutrition in children with CF.
DESIGN: BMI data were longitudinally collected from the CF Twin-Sibling Study and Cystic Fibrosis Foundation Patient Registry for twins and siblings from 2000 to 2010. A nutritional phenotype was derived for 1124 subjects by calculating the average BMI z score from 5-10 y of age (BMI-z(5to10)). The genetic contribution to the variation in BMI-z(5to10) (ie, heritability) was estimated by comparing the similarity of the phenotype in monozygous twins to that in dizygous twins and siblings. Linkage analysis identified potential modifier-gene loci.
RESULTS: The median BMI-z(5to10) was -0.07 (range: -3.89 to 2.30), which corresponded to the 47th CDC percentile. BMI-z(5to10) was negatively correlated with pancreatic insufficiency, history of meconium ileus, and female sex but positively correlated with later birth cohorts and lung function. Monozygous twins showed greater concordance for BMI-z(5to10) than did dizygous twins and siblings; heritability estimates from same-sex twin-only analyses ranged from 0.54 to 0.82. For 1010 subjects with pancreatic insufficiency, genome-wide significant linkage was identified on chromosomes 1p36.1 [log of odds (LOD): 5.3] and 5q14 (LOD: 5.1). These loci explained ≥16% and ≥15%, respectively, of the BMI variance.
CONCLUSIONS: The analysis of twins and siblings with CF indicates a prominent role for genes other than CFTR to BMI variation. Specifically, regions on chromosomes 1 and 5 appear to harbor genetic modifiers of substantial effect.
Authors:
Gia M Bradley; Scott M Blackman; Christopher P Watson; Vishal K Doshi; Garry R Cutting
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Twin Study     Date:  2012-11-07
Journal Detail:
Title:  The American journal of clinical nutrition     Volume:  96     ISSN:  1938-3207     ISO Abbreviation:  Am. J. Clin. Nutr.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-21     Completed Date:  2013-01-25     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  0376027     Medline TA:  Am J Clin Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1299-308     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Body Mass Index
Child Development*
Child, Preschool
Chromosomes, Human, Pair 1 / genetics*
Chromosomes, Human, Pair 5 / genetics*
Cystic Fibrosis / genetics*,  metabolism,  physiopathology
Cystic Fibrosis Transmembrane Conductance Regulator / genetics,  metabolism
Female
Genetic Loci
Genetic Variation*
Genome-Wide Association Study
Humans
Longitudinal Studies
Male
Nutritional Status*
Pancreas / physiopathology
Registries
Siblings
Twins, Dizygotic
Twins, Monozygotic
Grant Support
ID/Acronym/Agency:
5 T32 HD44355-8/HD/NICHD NIH HHS; DK076446/DK/NIDDK NIH HHS; HL068927/HL/NHLBI NIH HHS; K23 DK083551/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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