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Association between polymorphisms in leptin, leptin receptor, and β-adrenergic receptor genes and bone mineral density in postmenopausal Korean women

Lee, Hee Jun MD1; Kim, Hoon MD, PhD1; Ku, Seung-Yup MD, PhD1,2; Choi, Young Min MD, PhD1,2; Kim, Jong Hak MD, PhD3; Kim, Jung Gu MD, PhD1,2

doi: 10.1097/GME.0b013e31829366ed
Original Articles

Objective The purpose of this study was to investigate the association between single nucleotide polymorphisms in leptin (LEP), leptin receptor (LEPR), and β-adrenergic receptor (ADRB) genes and bone mineral density (BMD) in postmenopausal Korean women.

Methods LEP c.280G>A, LEPR c.326A>G, LEPR c.668A>G, LEPR c.1968G>C, LEPR c.2096C>T, ADRB2 c.46A>G, ADRB2 c.79C>G, ADRB2 c.718T>C, ADRB2 c.741G>T, ADRB2 c.769G>A, and ADRB3 c.190T>C polymorphisms were analyzed in 592 postmenopausal Korean women. Serum levels of leptin, soluble leptin receptor, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, bone alkaline phosphatase, and carboxy-terminal telopeptide of type I collagen were measured, and BMDs at the lumbar spine and femoral neck were also examined.

Results Among the polymorphisms measured, only the LEPR c.1968G>C polymorphism was found to be associated with BMD at the femoral neck, and higher BMD was observed with increasing number of G alleles (P = 0.04). Osteoporosis at the femoral neck was 3.27 and 3.89 times more frequently observed in the AG and GG genotypes than in the AA genotype in the ADRB2 c.46A>G polymorphism (P = 0.024 and P = 0.015, respectively). However, no significant differences in serum levels of leptin, soluble leptin receptor, free leptin index, osteoprotegerin, soluble receptor activator of the nuclear factor-κB ligand, and bone turnover markers were detected among single and haplotype genotypes.

Conclusions These results suggest that the LEPR c.1968G>C polymorphism may be one of the genetic factors affecting femoral neck BMD in postmenopausal Korean women and that an analysis of the ADRB2 c.46A>G polymorphism may be useful in identifying women at risk for osteoporosis at the femoral neck.

From the 1Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea; 2Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; and 3Department of Anesthesiology and Pain Medicine, School of Medicine, Ewha Woman’s University, Seoul, Korea.

Received January 30, 2013; revised and accepted March 18, 2013.

J.H.K. and J.G.K. contributed equally to this work as corresponding authors.

Funding/support: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology (2011-0022334).

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Jung Gu Kim, MD, PhD, Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yeungun-dong, Chongno-gu, Seoul 110-744, Korea. E-mail: kimjg@plaza.snu.ac.kr; Jong Hak Kim, MD, PhD, Department of Anesthesiology and Pain Medicine, Ewha Woman’s University, Mokdong Hospital, 911, Mok-dong, Yangcheon-gu, Seoul 158-710, Korea. E-mail: kjhanes@ewha.ac.kr

© 2014 by The North American Menopause Society.