A functional polymorphism in the PTHR1 promoter region is associated with adult height and BMD measured at the femoral neck in a large cohort of young caucasian women

Alfredo Scillitani, Carolyn Jang, Betty Y L Wong, Geoffrey N. Hendy, David E C Cole

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The parathyroid hormone type 1 receptor (PTHR1) mediates the actions of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHRP). Interacting with this receptor, PTHRP contributes to skeletal development through the regulation of chondrocyte proliferation and differentiation. Recently, a tetranucleotide repeat - (AAAG)n - In the P3 promoter of the PTHR1 gene has been shown to have functional activity in vitro, and homozygosity for (AAAG)6, or the 6/6 genotype, has been associated with greater adult height compared to the 5/5 genotype. In this study, we evaluated the association of (AAAG)n with height and bone mineral density (BMD) measured at lumbar spine (LS) and femoral neck (FN) in a cohort of 677 young caucasian women 18-35 years of age. Genomic DNA was amplified and genotyped by comparison with sequenced controls following electrophoretic separation through high-resolution polyacrylamide gels. Allele frequencies for (AAAG)n were: 76.8% (n=5); 20.9% (n=6); 1.8% (n=7); 0.18% (n=8); 0.27% (n=9); 0.08% (n=2), and there was no evidence for Hardy-Weinberg disequilibrium. Analysis of variance showed that subjects bearing one or two (AAAG)6 alleles (6/X & 6/6) were significantly taller (165.7±0.5 cm) than the others (X/X, 164.5±0.3 cm; P=0.034). This association was significant after adjusting for multiple covariates-current age, age at menarche, physical activity, smoking status, and intakes of caffeine and calcium. Comparison of genotype groups for BMD was not significant at LS, but BMD was significantly higher at FN in the group with at least one (AAAG)6 allele (adjusted means: 1.021±0.008 vs. 0.999±0.006 g/cm2, P=0.032). In conclusion, our data show that subjects bearing one or two (AAAG)6 alleles are taller than subjects without, reinforcing the notion that in vivo variation in promoter activity of the PTHR1 gene may be a relevant genetic influence on final adult height and BMD.

Original languageEnglish
Pages (from-to)416-421
Number of pages6
JournalHuman Genetics
Volume119
Issue number4
DOIs
Publication statusPublished - May 2006

Fingerprint

Parathyroid Hormone Receptor Type 1
Femur Neck
Genetic Promoter Regions
Bone Density
Parathyroid Hormone-Related Protein
Alleles
Genotype
Spine
Menarche
Chondrocytes
Caffeine
Parathyroid Hormone
Gene Frequency
Microsatellite Repeats
Genes
Analysis of Variance
Smoking
Exercise
Calcium
DNA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

A functional polymorphism in the PTHR1 promoter region is associated with adult height and BMD measured at the femoral neck in a large cohort of young caucasian women. / Scillitani, Alfredo; Jang, Carolyn; Wong, Betty Y L; Hendy, Geoffrey N.; Cole, David E C.

In: Human Genetics, Vol. 119, No. 4, 05.2006, p. 416-421.

Research output: Contribution to journalArticle

@article{85ec81ba3a8c42568debddacf0720e17,
title = "A functional polymorphism in the PTHR1 promoter region is associated with adult height and BMD measured at the femoral neck in a large cohort of young caucasian women",
abstract = "The parathyroid hormone type 1 receptor (PTHR1) mediates the actions of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHRP). Interacting with this receptor, PTHRP contributes to skeletal development through the regulation of chondrocyte proliferation and differentiation. Recently, a tetranucleotide repeat - (AAAG)n - In the P3 promoter of the PTHR1 gene has been shown to have functional activity in vitro, and homozygosity for (AAAG)6, or the 6/6 genotype, has been associated with greater adult height compared to the 5/5 genotype. In this study, we evaluated the association of (AAAG)n with height and bone mineral density (BMD) measured at lumbar spine (LS) and femoral neck (FN) in a cohort of 677 young caucasian women 18-35 years of age. Genomic DNA was amplified and genotyped by comparison with sequenced controls following electrophoretic separation through high-resolution polyacrylamide gels. Allele frequencies for (AAAG)n were: 76.8{\%} (n=5); 20.9{\%} (n=6); 1.8{\%} (n=7); 0.18{\%} (n=8); 0.27{\%} (n=9); 0.08{\%} (n=2), and there was no evidence for Hardy-Weinberg disequilibrium. Analysis of variance showed that subjects bearing one or two (AAAG)6 alleles (6/X & 6/6) were significantly taller (165.7±0.5 cm) than the others (X/X, 164.5±0.3 cm; P=0.034). This association was significant after adjusting for multiple covariates-current age, age at menarche, physical activity, smoking status, and intakes of caffeine and calcium. Comparison of genotype groups for BMD was not significant at LS, but BMD was significantly higher at FN in the group with at least one (AAAG)6 allele (adjusted means: 1.021±0.008 vs. 0.999±0.006 g/cm2, P=0.032). In conclusion, our data show that subjects bearing one or two (AAAG)6 alleles are taller than subjects without, reinforcing the notion that in vivo variation in promoter activity of the PTHR1 gene may be a relevant genetic influence on final adult height and BMD.",
author = "Alfredo Scillitani and Carolyn Jang and Wong, {Betty Y L} and Hendy, {Geoffrey N.} and Cole, {David E C}",
year = "2006",
month = "5",
doi = "10.1007/s00439-006-0155-8",
language = "English",
volume = "119",
pages = "416--421",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - A functional polymorphism in the PTHR1 promoter region is associated with adult height and BMD measured at the femoral neck in a large cohort of young caucasian women

AU - Scillitani, Alfredo

AU - Jang, Carolyn

AU - Wong, Betty Y L

AU - Hendy, Geoffrey N.

AU - Cole, David E C

PY - 2006/5

Y1 - 2006/5

N2 - The parathyroid hormone type 1 receptor (PTHR1) mediates the actions of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHRP). Interacting with this receptor, PTHRP contributes to skeletal development through the regulation of chondrocyte proliferation and differentiation. Recently, a tetranucleotide repeat - (AAAG)n - In the P3 promoter of the PTHR1 gene has been shown to have functional activity in vitro, and homozygosity for (AAAG)6, or the 6/6 genotype, has been associated with greater adult height compared to the 5/5 genotype. In this study, we evaluated the association of (AAAG)n with height and bone mineral density (BMD) measured at lumbar spine (LS) and femoral neck (FN) in a cohort of 677 young caucasian women 18-35 years of age. Genomic DNA was amplified and genotyped by comparison with sequenced controls following electrophoretic separation through high-resolution polyacrylamide gels. Allele frequencies for (AAAG)n were: 76.8% (n=5); 20.9% (n=6); 1.8% (n=7); 0.18% (n=8); 0.27% (n=9); 0.08% (n=2), and there was no evidence for Hardy-Weinberg disequilibrium. Analysis of variance showed that subjects bearing one or two (AAAG)6 alleles (6/X & 6/6) were significantly taller (165.7±0.5 cm) than the others (X/X, 164.5±0.3 cm; P=0.034). This association was significant after adjusting for multiple covariates-current age, age at menarche, physical activity, smoking status, and intakes of caffeine and calcium. Comparison of genotype groups for BMD was not significant at LS, but BMD was significantly higher at FN in the group with at least one (AAAG)6 allele (adjusted means: 1.021±0.008 vs. 0.999±0.006 g/cm2, P=0.032). In conclusion, our data show that subjects bearing one or two (AAAG)6 alleles are taller than subjects without, reinforcing the notion that in vivo variation in promoter activity of the PTHR1 gene may be a relevant genetic influence on final adult height and BMD.

AB - The parathyroid hormone type 1 receptor (PTHR1) mediates the actions of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHRP). Interacting with this receptor, PTHRP contributes to skeletal development through the regulation of chondrocyte proliferation and differentiation. Recently, a tetranucleotide repeat - (AAAG)n - In the P3 promoter of the PTHR1 gene has been shown to have functional activity in vitro, and homozygosity for (AAAG)6, or the 6/6 genotype, has been associated with greater adult height compared to the 5/5 genotype. In this study, we evaluated the association of (AAAG)n with height and bone mineral density (BMD) measured at lumbar spine (LS) and femoral neck (FN) in a cohort of 677 young caucasian women 18-35 years of age. Genomic DNA was amplified and genotyped by comparison with sequenced controls following electrophoretic separation through high-resolution polyacrylamide gels. Allele frequencies for (AAAG)n were: 76.8% (n=5); 20.9% (n=6); 1.8% (n=7); 0.18% (n=8); 0.27% (n=9); 0.08% (n=2), and there was no evidence for Hardy-Weinberg disequilibrium. Analysis of variance showed that subjects bearing one or two (AAAG)6 alleles (6/X & 6/6) were significantly taller (165.7±0.5 cm) than the others (X/X, 164.5±0.3 cm; P=0.034). This association was significant after adjusting for multiple covariates-current age, age at menarche, physical activity, smoking status, and intakes of caffeine and calcium. Comparison of genotype groups for BMD was not significant at LS, but BMD was significantly higher at FN in the group with at least one (AAAG)6 allele (adjusted means: 1.021±0.008 vs. 0.999±0.006 g/cm2, P=0.032). In conclusion, our data show that subjects bearing one or two (AAAG)6 alleles are taller than subjects without, reinforcing the notion that in vivo variation in promoter activity of the PTHR1 gene may be a relevant genetic influence on final adult height and BMD.

UR - http://www.scopus.com/inward/record.url?scp=33645746691&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645746691&partnerID=8YFLogxK

U2 - 10.1007/s00439-006-0155-8

DO - 10.1007/s00439-006-0155-8

M3 - Article

VL - 119

SP - 416

EP - 421

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 4

ER -