Association of polymorphisms in the leptin and leptin receptor genes with inflammatory mediators in patients with osteop
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ORIGINAL ARTICLE
Association of polymorphisms in the leptin and leptin receptor genes with inflammatory mediators in patients with osteoporosis Xing L. Ye • Chun F. Lu
Received: 22 October 2012 / Accepted: 2 February 2013 Ó Springer Science+Business Media New York 2013
Abstract Bone mass and inflammation are implicated in the pathogenesis of osteoporosis. We hypothesized that leptin and leptin receptor gene might be associated with osteoporosis by activating the inflammatory pathway. Therefore, we analyzed polymorphisms of the leptin (gene symbol, LEP) and leptin receptor (gene symbol, LEPR) genes and determined their associations with proinflammatory cytokine levels in patients with osteoporosis. We assessed polymorphisms in LEP (-2548G [ A) and LEPR (Lys109Arg, Gln223Arg, and Lys656Asn) and calculated odds ratios for the genotype and allele distributions between patients and controls. Serum leptin, soluble leptin receptor, interleukin (IL)-1, IL-6, IL-7, and tumor necrosis factor (TNF) levels were measured by enzyme-linked immunosorbent assays (ELISA) and were verified by in vitro lymphocyte proliferation assays and ELISAs. We found a higher frequency of the A allele for LEP at -2548 in patients with osteoporosis compared with the control group. The A allele was associated with differences in serum leptin, soluble leptin receptor, IL-1, IL-6, and TNF levels compared with the wild-type G allele (p \ 0.05). The G allele in Lys109Arg and Gln223Arg was associated with increased risk of osteoporosis and with differences in serum leptin, soluble leptin receptor, IL-1, IL-6, and TNF levels compared with the wild-type A allele (p \ 0.05). The Lys656Asn genotype was not associated with the risk of osteoporosis. In vitro lymphocyte proliferation assays and ELISAs confirmed these results. Polymorphisms in LEP and LEPR are associated with increased risk of
X. L. Ye (&) C. F. Lu P.E. Department, Zhejiang University of Science and Technology, Hangzhou 310023, Zhejiang, China e-mail: [email protected]
osteoporosis, possibly by increasing the expression of proinflammatory cytokines. Keywords Osteoporosis Leptin Polymorphism Inflammatory cytokines
Introduction Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of the microarchitecture of bone tissue [1, 2]. Although osteoporosis is generally considered to affect women, it is also very common in men. While the incidence of osteoporotic fractures in men is about half that in women [3], the mortality rate associated with hip fractures is considerably higher in elderly men than in women [4]. Osteoporosis is attributed to various factors, and bone mass is an important determinant in the development of osteoporosis [5]. Although environmental factors, such as nutrition and physical activity, may affect bone mass, genetic factors are the deciding determinants [6]. Polymorphisms in several genes, including RANK (TNFRSF11A; tumor necrosis factor receptor superfamily, member 11a), SP7 (osterix), and SOX6 (SRY [sex-determining region Y]-
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