Interleukin-6 Gene Polymorphism Is Related to Bone Mineral Density During and After Puberty in Healthy White Males: A Cross-Sectional and Longitudinal Study

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Abstract
Bone mineral density (BMD) is under strong genetic control and is the major determinant of fracture risk. The cytokine interleukin-6 (IL-6) is an important regulator of bone metabolism and is involved in mediating the effects of androgens and estrogens on bone. Recently, a G/C polymorphism in position -174 of the IL-6 gene promoter was found. We investigated this genetic polymorphism in relation to BMD during late puberty and to peak bone mass, in healthy white males. We identified the IL-6 genotypes (GG, GC, and CC) in 90 boys, age 16.9 +/- 0.3 years (mean +/- SD), using polymerase chain reaction (PCR). BMD (g/cm2) at the femoral neck, lumbar spine, and total body was measured using dual energy X-ray absorptiometry. The volumetric BMD (vBMD; mg/cm3) of the lumbar spine was estimated. Differences in BMD in relation to the genotypes were calculated using analysis of variance (ANOVA). Subjects with the CC genotype had 7.9% higher BMD of the femoral neck (p = 0.03), 7.0% higher BMD of the lumbar spine (p < 0.05), and 7.6% higher vBMD of the lumbar spine (p = 0.04), compared with their GG counterparts. Using multiple regression, the IL-6 genotypes were independently related to total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p < 0.05), neck BMD (CC > GG; p = 0.01), spine BMD (CC > GG; p = 0.01), and spine vBMD (CC > GG; p = 0.008). At age 19.3 +/- 0.7 years (mean +/- SD; 88 men) the IL-6 genotypes were still independent predictors for total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p = 0.03), spine BMD (CC > GG; p = 0.02), and spine vBMD (CC > GG; p = 0.003), while the IL-6 genotypes were not related to the increase in bone density seen after 2 years. We have shown that polymorphism of the IL-6 gene is an independent predictor of BMD during late puberty and of peak bone mass in healthy white men.