Association of interleukin-6 promoter variant with bone mineral density in pre-menopausal women

• Published in: Journal of human genetics Vol. 48; no. 5; pp. 243 - 248
• Main Authors: Chung, Hye Won, Seo, Jeong-Sun, Hur, Sung Eun, Kim, Hyung Lae, Kim, Jun Yeon, Jung, Ji Hyun, Kim, Lyoung Hyo, Park, Byung Lae, Shin, Hyoung Doo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.05.2003
• Subjects: Adult; Alleles; Asian Continental Ancestry Group - genetics; Bone density; Bone Density - genetics; Bone mineral density; Bone resorption; Chromosomes, Human, Pair 6; Cohort Studies; Cytokines; Female; Gene Frequency; Genetic Variation; Genotype; Health risk assessment; Heterozygotes; Homozygote; Humans; Immune response; Interleukin 6; Interleukin-6 - genetics; Menopause; Osteoporosis - etiology; Osteoporosis - genetics; Polymorphism, Single Nucleotide; Population genetics; Premenopause; Promoter Regions, Genetic; Single-nucleotide polymorphism
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1007/s10038-003-0020-8

Interleukin-6 (IL6) has many roles essential to the regulation of the immune response, hematopoiesis, and bone resorption. Three single-nucleotide polymorphisms (SNP) in the IL6 promoter region were genotyped by the single-base extension method. The frequencies of each SNP were 0.002 ( IL6-597 G--> A), 0.27 ( IL6-572 G--> C), and 0.002 ( IL6-174 G--> C) in a Korean population ( n=1,082). IL6-597 G--> A and IL6-174 G--> C were totally linked together ( d(2)=1) and showed very low allele frequencies (0.002), which are common in Caucasians. On the other hand, the frequency of the IL6-572 G--> C*C allele was much higher (0.27) than that in Caucasian populations (<0.07). One of the IL6 promoter SNPs, viz., IL6-572 G--> C, showed significant associations with bone mineral density (BMD), i.e., the C allele was associated with increased BMD ( P=0.02, co-dominant model; P=0.007, dominant model). The mean BMD was highest in homozygous C individuals (0.67+/-0.15), lowest in homozygous G individuals (0.58+/-0.19), and intermediate in heterozygotes (0.64+/-0.21). In the present study, we describe a variant in the IL6 promoter region that shows positive association with higher BMD in a gene-dose-dependent manner in pre-menopausal women.