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A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women.
Arthritis Rheum. 2001 Jan; 44(1):196-201.AR

Abstract

OBJECTIVE

To examine functional interleukin-6 (IL-6) -174 G-->C allelic variants in relation to bone turnover and bone mineral density (BMD) in postmenopausal women.

METHODS

Four hundred thirty-four healthy women living in the community (mean +/- SD age 71.7 +/- 5.7 years) were genotyped for the IL-6 -174 G-->C polymorphism. Serum levels of C-telopeptide of type I collagen (CTx), a marker of bone resorption, and osteocalcin (OC), a marker of bone formation, were determined. BMD at the hip and forearm was measured by dual-energy x-ray absorptiometry.

RESULTS

CTx levels differed significantly (P = 0.006) among IL-6 genotypes (mean +/- SEM 0.275 +/- 0.02 ng/ml, 0.325 +/- 0.01 ng/ml, and 0.356 +/- 0.02 ng/ml in women with the CC genotype [n = 68], the GC genotype [n = 204], and the GG genotype [n = 162], respectively). Compared with the GG group, age-adjusted odds ratios for high bone resorption were 0.65 (95% confidence interval [95% CI] 0.41-1.0, P = 0.06) and 0.37 (95% CI 0.18-0.73, P = 0.0047) in GC and CC subjects, respectively. In contrast, OC levels did not differ by genotype. BMD at the hip and forearm was 1.5-5% higher in CC subjects compared with GG subjects (P not significant). When the cohort was divided according to the median age (70.5 years), BMD was significantly decreased in older compared with younger postmenopausal women with the GG and GC genotypes (-9.6% on average; P < 0.01), but not in those with the CC genotype (-5.1% on average; P not significant).

CONCLUSION

Compared with the GC and GG IL-6 -174 G-->C genotypes, the CC genotype is associated with lower bone resorption and lesser decrease in bone mass in older postmenopausal women. These results suggest that IL-6 -174 G-->C alleles may be significant determinants of the risk for osteoporosis in elderly subjects.

Authors+Show Affiliations

Division of Bone and Mineral Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11212160

Citation

Ferrari, S L., et al. "A Functional Polymorphic Variant in the Interleukin-6 Gene Promoter Associated With Low Bone Resorption in Postmenopausal Women." Arthritis and Rheumatism, vol. 44, no. 1, 2001, pp. 196-201.
Ferrari SL, Garnero P, Emond S, et al. A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women. Arthritis Rheum. 2001;44(1):196-201.
Ferrari, S. L., Garnero, P., Emond, S., Montgomery, H., Humphries, S. E., & Greenspan, S. L. (2001). A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women. Arthritis and Rheumatism, 44(1), 196-201.
Ferrari SL, et al. A Functional Polymorphic Variant in the Interleukin-6 Gene Promoter Associated With Low Bone Resorption in Postmenopausal Women. Arthritis Rheum. 2001;44(1):196-201. PubMed PMID: 11212160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women. AU - Ferrari,S L, AU - Garnero,P, AU - Emond,S, AU - Montgomery,H, AU - Humphries,S E, AU - Greenspan,S L, PY - 2001/2/24/pubmed PY - 2001/3/10/medline PY - 2001/2/24/entrez SP - 196 EP - 201 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 44 IS - 1 N2 - OBJECTIVE: To examine functional interleukin-6 (IL-6) -174 G-->C allelic variants in relation to bone turnover and bone mineral density (BMD) in postmenopausal women. METHODS: Four hundred thirty-four healthy women living in the community (mean +/- SD age 71.7 +/- 5.7 years) were genotyped for the IL-6 -174 G-->C polymorphism. Serum levels of C-telopeptide of type I collagen (CTx), a marker of bone resorption, and osteocalcin (OC), a marker of bone formation, were determined. BMD at the hip and forearm was measured by dual-energy x-ray absorptiometry. RESULTS: CTx levels differed significantly (P = 0.006) among IL-6 genotypes (mean +/- SEM 0.275 +/- 0.02 ng/ml, 0.325 +/- 0.01 ng/ml, and 0.356 +/- 0.02 ng/ml in women with the CC genotype [n = 68], the GC genotype [n = 204], and the GG genotype [n = 162], respectively). Compared with the GG group, age-adjusted odds ratios for high bone resorption were 0.65 (95% confidence interval [95% CI] 0.41-1.0, P = 0.06) and 0.37 (95% CI 0.18-0.73, P = 0.0047) in GC and CC subjects, respectively. In contrast, OC levels did not differ by genotype. BMD at the hip and forearm was 1.5-5% higher in CC subjects compared with GG subjects (P not significant). When the cohort was divided according to the median age (70.5 years), BMD was significantly decreased in older compared with younger postmenopausal women with the GG and GC genotypes (-9.6% on average; P < 0.01), but not in those with the CC genotype (-5.1% on average; P not significant). CONCLUSION: Compared with the GC and GG IL-6 -174 G-->C genotypes, the CC genotype is associated with lower bone resorption and lesser decrease in bone mass in older postmenopausal women. These results suggest that IL-6 -174 G-->C alleles may be significant determinants of the risk for osteoporosis in elderly subjects. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/11212160/A_functional_polymorphic_variant_in_the_interleukin_6_gene_promoter_associated_with_low_bone_resorption_in_postmenopausal_women_ L2 - https://doi.org/10.1002/1529-0131(200101)44:1&lt;196::AID-ANR26&gt;3.0.CO;2-5 DB - PRIME DP - Unbound Medicine ER -