Association between a Polymorphism Affecting an AP1 Binding Site in the Promoter of the TCIRG1 Gene and Bone Mass in Women

C. Sobacchi, P. Vezzoni, D. M. Reid, F. E A McGuigan, A. Frattini, M. Mirolo, Omar Al Bagha, A. Musio, A. Villa, S. H. Ralston

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The TCIRG1 gene encodes a component of the osteoclast vacuolar proton pump and previous work has shown that inactivating mutations of the TCIRG1 cause autosomal recessive osteopetrosis. In order to determine whether allelic variation in TCIRG1 contributes to the regulation of bone mineral density (BMD) in normal individuals, we studied the relationship between polymorphisms of TCIRG1 and BMD in a population-based cohort of 739 perimenopausal women. Five common polymorphisms were identified: two in the promoter, a conservative change within exon 4, one within intron 4 and one within intron 11. One of the promoter polymorphisms (G-1102A) lay within a consensus recognition site for the AP1 transcription factor. There was a significant association between the G-1102A genotype and BMD at the lumbar spine (P = 0.01) and femoral neck (P = 0.03). The association remained significant after correcting for age, weight, height, menopausal status/HRT use and smoking (P = 0.008 for spine BMD and P = 0.03 for hip BMD), and homozygotes for the -1100 "G" allele had BMD values significantly higher than individuals who carried the -1100 "A" allele at both spine (P = 0.007) and hip (P = 0.047). Subgroup analysis showed that the association between G-1102A and BMD was restricted to premenopausal women who comprised 50.6% of the study group. None of the other polymorphisms or haplotypes were significantly associated with BMD in the study group as a whole or in any subgroup. Functional studies will need to be performed to determine the mechanisms that underlie this association, but we conclude that, in this relatively large population, allelic variation at the G-1102A site of TCIRG1 accounts for part of the heritable component of BMD in Scottish women, possibly by affecting peak bone mass.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalCalcified Tissue International
Volume74
Issue number1
DOIs
Publication statusPublished - Jan 2004
Externally publishedYes

Fingerprint

Bone Density
Binding Sites
Bone and Bones
Genes
Spine
Introns
Alleles
Pelvic Bones
Osteopetrosis
Proton Pumps
Femur Neck
Homozygote
Osteoclasts
Haplotypes
Population
Hip
Exons
Consensus
Transcription Factors
Smoking

Keywords

  • BMD
  • Polymorphisms
  • Premenopause
  • TCIRG1 gene

ASJC Scopus subject areas

  • Endocrinology

Cite this

Sobacchi, C., Vezzoni, P., Reid, D. M., McGuigan, F. E. A., Frattini, A., Mirolo, M., ... Ralston, S. H. (2004). Association between a Polymorphism Affecting an AP1 Binding Site in the Promoter of the TCIRG1 Gene and Bone Mass in Women. Calcified Tissue International, 74(1), 35-41. https://doi.org/10.1007/s00223-002-0004-2

Association between a Polymorphism Affecting an AP1 Binding Site in the Promoter of the TCIRG1 Gene and Bone Mass in Women. / Sobacchi, C.; Vezzoni, P.; Reid, D. M.; McGuigan, F. E A; Frattini, A.; Mirolo, M.; Al Bagha, Omar; Musio, A.; Villa, A.; Ralston, S. H.

In: Calcified Tissue International, Vol. 74, No. 1, 01.2004, p. 35-41.

Research output: Contribution to journalArticle

Sobacchi, C, Vezzoni, P, Reid, DM, McGuigan, FEA, Frattini, A, Mirolo, M, Al Bagha, O, Musio, A, Villa, A & Ralston, SH 2004, 'Association between a Polymorphism Affecting an AP1 Binding Site in the Promoter of the TCIRG1 Gene and Bone Mass in Women', Calcified Tissue International, vol. 74, no. 1, pp. 35-41. https://doi.org/10.1007/s00223-002-0004-2
Sobacchi, C. ; Vezzoni, P. ; Reid, D. M. ; McGuigan, F. E A ; Frattini, A. ; Mirolo, M. ; Al Bagha, Omar ; Musio, A. ; Villa, A. ; Ralston, S. H. / Association between a Polymorphism Affecting an AP1 Binding Site in the Promoter of the TCIRG1 Gene and Bone Mass in Women. In: Calcified Tissue International. 2004 ; Vol. 74, No. 1. pp. 35-41.
@article{f4b782d3dad3450f88e1b5c346783331,
title = "Association between a Polymorphism Affecting an AP1 Binding Site in the Promoter of the TCIRG1 Gene and Bone Mass in Women",
abstract = "The TCIRG1 gene encodes a component of the osteoclast vacuolar proton pump and previous work has shown that inactivating mutations of the TCIRG1 cause autosomal recessive osteopetrosis. In order to determine whether allelic variation in TCIRG1 contributes to the regulation of bone mineral density (BMD) in normal individuals, we studied the relationship between polymorphisms of TCIRG1 and BMD in a population-based cohort of 739 perimenopausal women. Five common polymorphisms were identified: two in the promoter, a conservative change within exon 4, one within intron 4 and one within intron 11. One of the promoter polymorphisms (G-1102A) lay within a consensus recognition site for the AP1 transcription factor. There was a significant association between the G-1102A genotype and BMD at the lumbar spine (P = 0.01) and femoral neck (P = 0.03). The association remained significant after correcting for age, weight, height, menopausal status/HRT use and smoking (P = 0.008 for spine BMD and P = 0.03 for hip BMD), and homozygotes for the -1100 {"}G{"} allele had BMD values significantly higher than individuals who carried the -1100 {"}A{"} allele at both spine (P = 0.007) and hip (P = 0.047). Subgroup analysis showed that the association between G-1102A and BMD was restricted to premenopausal women who comprised 50.6{\%} of the study group. None of the other polymorphisms or haplotypes were significantly associated with BMD in the study group as a whole or in any subgroup. Functional studies will need to be performed to determine the mechanisms that underlie this association, but we conclude that, in this relatively large population, allelic variation at the G-1102A site of TCIRG1 accounts for part of the heritable component of BMD in Scottish women, possibly by affecting peak bone mass.",
keywords = "BMD, Polymorphisms, Premenopause, TCIRG1 gene",
author = "C. Sobacchi and P. Vezzoni and Reid, {D. M.} and McGuigan, {F. E A} and A. Frattini and M. Mirolo and {Al Bagha}, Omar and A. Musio and A. Villa and Ralston, {S. H.}",
year = "2004",
month = "1",
doi = "10.1007/s00223-002-0004-2",
language = "English",
volume = "74",
pages = "35--41",
journal = "Calcified Tissue International",
issn = "0171-967X",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Association between a Polymorphism Affecting an AP1 Binding Site in the Promoter of the TCIRG1 Gene and Bone Mass in Women

AU - Sobacchi, C.

AU - Vezzoni, P.

AU - Reid, D. M.

AU - McGuigan, F. E A

AU - Frattini, A.

AU - Mirolo, M.

AU - Al Bagha, Omar

AU - Musio, A.

AU - Villa, A.

AU - Ralston, S. H.

PY - 2004/1

Y1 - 2004/1

N2 - The TCIRG1 gene encodes a component of the osteoclast vacuolar proton pump and previous work has shown that inactivating mutations of the TCIRG1 cause autosomal recessive osteopetrosis. In order to determine whether allelic variation in TCIRG1 contributes to the regulation of bone mineral density (BMD) in normal individuals, we studied the relationship between polymorphisms of TCIRG1 and BMD in a population-based cohort of 739 perimenopausal women. Five common polymorphisms were identified: two in the promoter, a conservative change within exon 4, one within intron 4 and one within intron 11. One of the promoter polymorphisms (G-1102A) lay within a consensus recognition site for the AP1 transcription factor. There was a significant association between the G-1102A genotype and BMD at the lumbar spine (P = 0.01) and femoral neck (P = 0.03). The association remained significant after correcting for age, weight, height, menopausal status/HRT use and smoking (P = 0.008 for spine BMD and P = 0.03 for hip BMD), and homozygotes for the -1100 "G" allele had BMD values significantly higher than individuals who carried the -1100 "A" allele at both spine (P = 0.007) and hip (P = 0.047). Subgroup analysis showed that the association between G-1102A and BMD was restricted to premenopausal women who comprised 50.6% of the study group. None of the other polymorphisms or haplotypes were significantly associated with BMD in the study group as a whole or in any subgroup. Functional studies will need to be performed to determine the mechanisms that underlie this association, but we conclude that, in this relatively large population, allelic variation at the G-1102A site of TCIRG1 accounts for part of the heritable component of BMD in Scottish women, possibly by affecting peak bone mass.

AB - The TCIRG1 gene encodes a component of the osteoclast vacuolar proton pump and previous work has shown that inactivating mutations of the TCIRG1 cause autosomal recessive osteopetrosis. In order to determine whether allelic variation in TCIRG1 contributes to the regulation of bone mineral density (BMD) in normal individuals, we studied the relationship between polymorphisms of TCIRG1 and BMD in a population-based cohort of 739 perimenopausal women. Five common polymorphisms were identified: two in the promoter, a conservative change within exon 4, one within intron 4 and one within intron 11. One of the promoter polymorphisms (G-1102A) lay within a consensus recognition site for the AP1 transcription factor. There was a significant association between the G-1102A genotype and BMD at the lumbar spine (P = 0.01) and femoral neck (P = 0.03). The association remained significant after correcting for age, weight, height, menopausal status/HRT use and smoking (P = 0.008 for spine BMD and P = 0.03 for hip BMD), and homozygotes for the -1100 "G" allele had BMD values significantly higher than individuals who carried the -1100 "A" allele at both spine (P = 0.007) and hip (P = 0.047). Subgroup analysis showed that the association between G-1102A and BMD was restricted to premenopausal women who comprised 50.6% of the study group. None of the other polymorphisms or haplotypes were significantly associated with BMD in the study group as a whole or in any subgroup. Functional studies will need to be performed to determine the mechanisms that underlie this association, but we conclude that, in this relatively large population, allelic variation at the G-1102A site of TCIRG1 accounts for part of the heritable component of BMD in Scottish women, possibly by affecting peak bone mass.

KW - BMD

KW - Polymorphisms

KW - Premenopause

KW - TCIRG1 gene

UR - http://www.scopus.com/inward/record.url?scp=0842283935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0842283935&partnerID=8YFLogxK

U2 - 10.1007/s00223-002-0004-2

DO - 10.1007/s00223-002-0004-2

M3 - Article

C2 - 14523594

AN - SCOPUS:0842283935

VL - 74

SP - 35

EP - 41

JO - Calcified Tissue International

JF - Calcified Tissue International

SN - 0171-967X

IS - 1

ER -