Journal of Korean Endocrine Society 2004;19(2):181-193.
Published online April 1, 2004.
The Effects of C161-->T Polymorphisms in Exon 6 of Peroxisome Proliferator-Activated Receptor- Gene on Bone Mineral Metabolism and Serum Osteoprotegerin Levels in Healthy Korean Middle-aged Men.
Eun Jung Rhee, Won Young Lee, Se Yeon Kim, Eun Sook Oh, Ki Hyun Baek, Ki Won Oh, Kyung Chang Park, Ki Ok Han, Hyun Koo Yoon, Moo Il Kang, Sun Woo Kim
1Department of Internal Medicine, College of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
2Research Institute of Medical Science, College of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea.
3Department of Internal Medicine, Miz Medi Hospital, Seoul, Korea.
4Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea.
5Department of Internal Medicine, Hallym University, Chunchon, Korea.
6Department of Internal Medicine, Samsung Cheil Hospital, Seoul, Korea.
The peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear receptor family known to be involved in adipocyte differentiation. Recent studies have revealed the inhibitory role of PPAR in osteoblastogenesis, which suggests its possibility as a candidate gene for osteoporosis. The frequency of C161-->T substitution in exon 6 of PPAR was observed in Korean men and the association of different genotypes with bone turnover markers, bone mineral density (BMD) and serum osteoprotegerin (OPG), which play inhibitory roles in osteoclastogenesis, examined. METHODS: In 72 healthy Korean men (mean age 54.5 6.4 yrs; range 42~69 yrs), anthropometric measurements, and lumbar spine and femoral neck BMD, and bone turnover markers, such as alkaline phosphatase (ALP), serum calcium, phosphorus, osteocalcin and cross-linked C-telopeptides of type I collagen (ICTP) measurements were performed. The levels of serum testosterone, estradiol and insulin-like growth factor (IGF-I), and those of serum OPG levels, were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) method. The DNAs were extracted from the samples, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the sequencing of the products were performed to confirm the substitution. RESULTS: The allele frequencies were 0.799 and 0.201 for the C and T allele, respectively, which were in Hardy-Weinberg equilibrium (p=0.80). Subjects with the CT genotype were older and those with the T allele showed higher blood pressure levels and lower body mass indices (p<0.05) than those with the CC genotypes. There were no differences in the bone turnover markers between the different genotypes (p>0.05). The levels of serum testosterone, estradiol, IGF-I and OPG were not different among the different genotype groups (p>0.05). The lumbar, femoral neck BMD (g/cm2) and T scores were significantly lower in subjects with T alleles, and those with CT genotypes showed the lowest BMD values (p<0.05). When the subjects were divided into 3 groups, i.e., normal, osteopenic and osteoporotic groups, according to the lumbar spine BMD, the group with the T allele had a significantly higher prevalence of osteopenia and smaller numbers with normal BMD than those with the CC genotype (p=0.032). CONCLUSION: The frequencies of the C161-->T substitution in exon 6 of the PPAR gene in Korean men were similar to those observed in other races, and those with the T alleles showed significantly lower BMD values. These data imply the PPAR gene might be a candidate gene for the pathogenesis of osteoporosis
Key Words: PPAR, Bone mineral density, Osteoprotegerin
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