title: Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: the HERITAGE family study.
abstract: We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.
authors.affiliation: Human Genomics Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808-4124, USA. lakkat@pbrc.edu
authors.forename: Timo A
authors.initials: TA
authors.lastname: Lakka
authors.forename: Tuomo
authors.initials: T
authors.lastname: Rankinen
authors.forename: S John
authors.initials: SJ
authors.lastname: Weisnagel
authors.forename: Yvon C
authors.initials: YC
authors.lastname: Chagnon
authors.forename: Hanna-Maaria
authors.initials: HM
authors.lastname: Lakka
authors.forename: Olavi
authors.initials: O
authors.lastname: Ukkola
authors.forename: Normand
authors.initials: N
authors.lastname: Boulé
authors.forename: Treva
authors.initials: T
authors.lastname: Rice
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Leon
authors.forename: James S
authors.initials: JS
authors.lastname: Skinner
authors.forename: Jack H
authors.initials: JH
authors.lastname: Wilmore
authors.forename: D C
authors.initials: DC
authors.lastname: Rao
authors.forename: Richard
authors.initials: R
authors.lastname: Bergman
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
mesh_terms: D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D015444:Exercise / Q000502:physiology*; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D044465:White People / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D005947:Glucose