Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women

K. Lian, L. Lui, J. M. Zmuda, M. C. Nevitt, M. C. Hochberg, J. M. Lee, J. Li, Nancy E Lane

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Abstract

Purpose: This study evaluated the association between polymorphisms in the estrogen receptor (ER) alpha gene (ESR1) and prevalent and incident radiographic hip osteoarthritis (RHOA) in a large, well-defined prospective cohort of elderly Caucasian women. Methods: Prevalent and incident RHOA was evaluated from all available pelvis X-rays obtained from the Study of Osteoporotic Fractures at baseline and after a mean of 8.3 years. Evaluable DNA samples were available from 4746 of these subjects. RHOA cases were defined by published methods. The ESR1 polymorphisms at intron I (Pvu II for a T/C substitution and Xba I for an A/G substitution) were genotyped in the context of a multiplex polymerase chain reaction (PCR) amplification followed by allele-specific single nucleotide polymorphism (SNP) detection with immobilized oligonucleotide probes in linear arrays. Multiple logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) associated with the T/C and A/G polymorphisms. Results: RHOA was present in 12.1% of subjects, of whom 325 had joint space narrowing (JSN) score ≥3 and 130 had an osteophyte score ≥2 and JSN score ≥2. There was a significant reduction in the odds of prevalent RHOA for individuals with the C/C compared to T/T genotype at the Pvu II site with an OR of 0.71 (95% CI: 0.55-0.92) (P = 0.01). Adjustments for age, weight, height, hip Bone mineral density (BMD) and estrogen use did not alter the relationship between the C/C genotype and reduced risk of RHOA, with an OR of 0.71 (95% CI: 0.54-0.94) (P = 0.01). The risk of incident RHOA was reduced for the Pvu II C/C compared to the T/T genotype (P = 0.11). Also, the reduced risk of incident RHOA in C/C subjects varied by estrogen use. There was no association between the Xba I G/G or G/A genotypes and RHOA with OR of 0.82 (95% CI: 0.61-1.10) (P = 0.19) compared to women with A/A genotype. Conclusions: We conclude that the C/C genotype of the ER alpha Pvu II polymorphism was associated with a modestly reduced risk of prevalent and incident RHOA in elderly Caucasian women. Additional work is required to understand how the intron I ESR1 polymorphism may alter joint degeneration.

Original languageEnglish (US)
Pages (from-to)972-978
Number of pages7
JournalOsteoarthritis and Cartilage
Volume15
Issue number8
DOIs
StatePublished - Aug 2007

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Hip Osteoarthritis
Estrogen Receptor alpha
Polymorphism
Genotype
Odds Ratio
Confidence Intervals
Substitution reactions
Association reactions
Joints
Oligonucleotides
Polymerase chain reaction
Introns
Nucleotides
Estrogens
Amplification
Immobilized Nucleic Acids
Logistics
Pelvic Bones
Bone
DNA

Keywords

  • Estrogen receptors
  • Osteoarthritis
  • Polymorphisms

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women. / Lian, K.; Lui, L.; Zmuda, J. M.; Nevitt, M. C.; Hochberg, M. C.; Lee, J. M.; Li, J.; Lane, Nancy E.

In: Osteoarthritis and Cartilage, Vol. 15, No. 8, 08.2007, p. 972-978.

Research output: Contribution to journalArticle

Lian, K. ; Lui, L. ; Zmuda, J. M. ; Nevitt, M. C. ; Hochberg, M. C. ; Lee, J. M. ; Li, J. ; Lane, Nancy E. / Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women. In: Osteoarthritis and Cartilage. 2007 ; Vol. 15, No. 8. pp. 972-978.
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abstract = "Purpose: This study evaluated the association between polymorphisms in the estrogen receptor (ER) alpha gene (ESR1) and prevalent and incident radiographic hip osteoarthritis (RHOA) in a large, well-defined prospective cohort of elderly Caucasian women. Methods: Prevalent and incident RHOA was evaluated from all available pelvis X-rays obtained from the Study of Osteoporotic Fractures at baseline and after a mean of 8.3 years. Evaluable DNA samples were available from 4746 of these subjects. RHOA cases were defined by published methods. The ESR1 polymorphisms at intron I (Pvu II for a T/C substitution and Xba I for an A/G substitution) were genotyped in the context of a multiplex polymerase chain reaction (PCR) amplification followed by allele-specific single nucleotide polymorphism (SNP) detection with immobilized oligonucleotide probes in linear arrays. Multiple logistic regression was performed to estimate odds ratios (ORs) and 95{\%} confidence intervals (95{\%} CI) associated with the T/C and A/G polymorphisms. Results: RHOA was present in 12.1{\%} of subjects, of whom 325 had joint space narrowing (JSN) score ≥3 and 130 had an osteophyte score ≥2 and JSN score ≥2. There was a significant reduction in the odds of prevalent RHOA for individuals with the C/C compared to T/T genotype at the Pvu II site with an OR of 0.71 (95{\%} CI: 0.55-0.92) (P = 0.01). Adjustments for age, weight, height, hip Bone mineral density (BMD) and estrogen use did not alter the relationship between the C/C genotype and reduced risk of RHOA, with an OR of 0.71 (95{\%} CI: 0.54-0.94) (P = 0.01). The risk of incident RHOA was reduced for the Pvu II C/C compared to the T/T genotype (P = 0.11). Also, the reduced risk of incident RHOA in C/C subjects varied by estrogen use. There was no association between the Xba I G/G or G/A genotypes and RHOA with OR of 0.82 (95{\%} CI: 0.61-1.10) (P = 0.19) compared to women with A/A genotype. Conclusions: We conclude that the C/C genotype of the ER alpha Pvu II polymorphism was associated with a modestly reduced risk of prevalent and incident RHOA in elderly Caucasian women. Additional work is required to understand how the intron I ESR1 polymorphism may alter joint degeneration.",
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T1 - Estrogen receptor alpha genotype is associated with a reduced prevalence of radiographic hip osteoarthritis in elderly Caucasian women

AU - Lian, K.

AU - Lui, L.

AU - Zmuda, J. M.

AU - Nevitt, M. C.

AU - Hochberg, M. C.

AU - Lee, J. M.

AU - Li, J.

AU - Lane, Nancy E

PY - 2007/8

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N2 - Purpose: This study evaluated the association between polymorphisms in the estrogen receptor (ER) alpha gene (ESR1) and prevalent and incident radiographic hip osteoarthritis (RHOA) in a large, well-defined prospective cohort of elderly Caucasian women. Methods: Prevalent and incident RHOA was evaluated from all available pelvis X-rays obtained from the Study of Osteoporotic Fractures at baseline and after a mean of 8.3 years. Evaluable DNA samples were available from 4746 of these subjects. RHOA cases were defined by published methods. The ESR1 polymorphisms at intron I (Pvu II for a T/C substitution and Xba I for an A/G substitution) were genotyped in the context of a multiplex polymerase chain reaction (PCR) amplification followed by allele-specific single nucleotide polymorphism (SNP) detection with immobilized oligonucleotide probes in linear arrays. Multiple logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) associated with the T/C and A/G polymorphisms. Results: RHOA was present in 12.1% of subjects, of whom 325 had joint space narrowing (JSN) score ≥3 and 130 had an osteophyte score ≥2 and JSN score ≥2. There was a significant reduction in the odds of prevalent RHOA for individuals with the C/C compared to T/T genotype at the Pvu II site with an OR of 0.71 (95% CI: 0.55-0.92) (P = 0.01). Adjustments for age, weight, height, hip Bone mineral density (BMD) and estrogen use did not alter the relationship between the C/C genotype and reduced risk of RHOA, with an OR of 0.71 (95% CI: 0.54-0.94) (P = 0.01). The risk of incident RHOA was reduced for the Pvu II C/C compared to the T/T genotype (P = 0.11). Also, the reduced risk of incident RHOA in C/C subjects varied by estrogen use. There was no association between the Xba I G/G or G/A genotypes and RHOA with OR of 0.82 (95% CI: 0.61-1.10) (P = 0.19) compared to women with A/A genotype. Conclusions: We conclude that the C/C genotype of the ER alpha Pvu II polymorphism was associated with a modestly reduced risk of prevalent and incident RHOA in elderly Caucasian women. Additional work is required to understand how the intron I ESR1 polymorphism may alter joint degeneration.

AB - Purpose: This study evaluated the association between polymorphisms in the estrogen receptor (ER) alpha gene (ESR1) and prevalent and incident radiographic hip osteoarthritis (RHOA) in a large, well-defined prospective cohort of elderly Caucasian women. Methods: Prevalent and incident RHOA was evaluated from all available pelvis X-rays obtained from the Study of Osteoporotic Fractures at baseline and after a mean of 8.3 years. Evaluable DNA samples were available from 4746 of these subjects. RHOA cases were defined by published methods. The ESR1 polymorphisms at intron I (Pvu II for a T/C substitution and Xba I for an A/G substitution) were genotyped in the context of a multiplex polymerase chain reaction (PCR) amplification followed by allele-specific single nucleotide polymorphism (SNP) detection with immobilized oligonucleotide probes in linear arrays. Multiple logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) associated with the T/C and A/G polymorphisms. Results: RHOA was present in 12.1% of subjects, of whom 325 had joint space narrowing (JSN) score ≥3 and 130 had an osteophyte score ≥2 and JSN score ≥2. There was a significant reduction in the odds of prevalent RHOA for individuals with the C/C compared to T/T genotype at the Pvu II site with an OR of 0.71 (95% CI: 0.55-0.92) (P = 0.01). Adjustments for age, weight, height, hip Bone mineral density (BMD) and estrogen use did not alter the relationship between the C/C genotype and reduced risk of RHOA, with an OR of 0.71 (95% CI: 0.54-0.94) (P = 0.01). The risk of incident RHOA was reduced for the Pvu II C/C compared to the T/T genotype (P = 0.11). Also, the reduced risk of incident RHOA in C/C subjects varied by estrogen use. There was no association between the Xba I G/G or G/A genotypes and RHOA with OR of 0.82 (95% CI: 0.61-1.10) (P = 0.19) compared to women with A/A genotype. Conclusions: We conclude that the C/C genotype of the ER alpha Pvu II polymorphism was associated with a modestly reduced risk of prevalent and incident RHOA in elderly Caucasian women. Additional work is required to understand how the intron I ESR1 polymorphism may alter joint degeneration.

KW - Estrogen receptors

KW - Osteoarthritis

KW - Polymorphisms

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