A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women.
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).


CONCLUSIONS
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.
Ferrari
S L
SL
Division of Bone and Mineral Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Garnero
P
P
Emond
S
S
Montgomery
H
H
Humphries
S E
SE
Greenspan
S L
SL
D000368:Aged; D015519:Bone Density / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics*; D015331:Cohort Studies; D003094:Collagen / Q000097:blood; D005260:Female; D014644:Genetic Variation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D017698:Postmenopause / Q000235:genetics; D011401:Promoter Regions, Genetic
D015850:Interleukin-6; D003094:Collagen