title: Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphisms.
abstract: OBJECTIVE
  Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress, often with dominant inheritance. It is likely that one or more genes will be associated with CDGP. Possible candidates are the leptin (L) and the leptin receptor (LR) genes, as the leptin axis links nutritional status to pubertal development. This study has assessed whether a) L or LR gene polymorphisms were associated with CDGP and b) the CDGP phenotype was influenced by these polymorphisms.
  
  
  METHODS
  Case-control and transmission disequilibrium tests were used to test genetic association of L and LR polymorphisms with CDGP.
  
  
  METHODS
  We genotyped L (3'CTTT repeat) and LR polymorphisms (Gln > Arg substitution, exon 6) in 81 CDGP children and 94 controls in the UK and 88 CDGP children from the US and assessed the effect of genotype on their anthropometric characteristics.
  
  
  RESULTS
  There was no association of these L or LR gene polymorphisms with CDGP. There was no difference in height or bone age delay within L or LR genotypes. However, UK CDGP children homozygous for the L short allele were heavier than heterozygotes and long allele homozygotes, with a similar trend in the US cohort. UK CDGP children with severe pubertal delay, who were thin, had significantly greater bone age delay and an increased frequency of parental pubertal delay than other groups and were less likely to be L short allele homozygotes.
  
  
  CONCLUSIONS
  There was no association of specific L or LR polymorphisms with CDGP, but L short allele carriage influenced the phenotype within CDGP.
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, UK.
authors.forename: Indraneel
authors.initials: I
authors.lastname: Banerjee
authors.forename: Julie A
authors.initials: JA
authors.lastname: Trueman
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hall
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Leena
authors.initials: L
authors.lastname: Patel
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Whatmore
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Read
authors.forename: Mark R
authors.initials: MR
authors.lastname: Palmert
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clayton
mesh_terms: D000293:Adolescent; D000483:Alleles; D000886:Anthropometry; D001827:Body Height / Q000502:physiology; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D001846:Bone Development / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006128:Growth / Q000235:genetics*; D006801:Humans; D020738:Leptin / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009752:Nutritional Status; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011628:Puberty, Delayed / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006113:United Kingdom; D014481:United States
chemical_list: C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D004247:DNA