Phenotypic variation in constitutional delay of growth and puberty: Relationship to specific leptin and leptin receptor gene polymorphisms

Indraneel Banerjee, Julie A. Trueman, Catherine M. Hall, David A. Price, Leena Patel, Andrew J. Whatmore, Joel N. Hirschhorn, Andrew P. Read, Mark R. Palmert, Peter E. Clayton

    Research output: Contribution to journalArticlepeer-review


    Objectives: 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. Design: 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. © 2006 Society of the European Journal of Endocrinology.
    Original languageEnglish
    Pages (from-to)121-126
    Number of pages5
    JournalEuropean Journal of Endocrinology
    Issue number1
    Publication statusPublished - Jul 2006


    • Adolescent
    • Alleles
    • Anthropometry
    • physiology: Body Height
    • Body Mass Index
    • physiology: Body Weight
    • genetics: Bone Development
    • Case-Control Studies
    • Child
    • Chromatography, High Pressure Liquid
    • genetics: DNA
    • Female
    • Genotype
    • Great Britain
    • genetics: Growth
    • Humans
    • genetics: Leptin
    • genetics: Linkage Disequilibrium
    • Male
    • Nutritional Status
    • Phenotype
    • genetics: Polymorphism, Genetic
    • genetics: Puberty, Delayed
    • genetics: Receptors, Cell Surface
    • Receptors, Leptin
    • Reverse Transcriptase Polymerase Chain Reaction
    • United States


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