LEPTIN A19G POLYMORPHISM AND LEPTIN RECEPTOR Gln223Arg AND Lys109Arg POLYMORPHISMSIN POSTMENOPAUSAL OSTEOPOROSIS
https://doi.org/10.14412/1995-4484-2010-727
Abstract
Objective: to study an association of leptin (LEP) A19G polymorphism and leptin receptor (LEPR) Gln223Arg AND Lys109Arg polymorphisms with the predilection for postmenopausal osteoporosis (OP).
Subjects and methods. PCR analysis was used to examine the polymorphisms among 428 women (254 patients with OP and 174 healthy women). The anthropometric, densitometric, and biochemical markers of bone remodeling and standard clinical and biochemical parameters were studied.
Results. Statistically significant differences were found in the distribution of the genotypes of LEP A19G polymorphism between the women with OP and the controls (χ2 = 9.41; p = 0.009). In the patients with OP, the 19GG genotype frequency was significantly higher than that in the controls [OR = 2.0; 95% confidence interval (CI) 1.13-3.52 (p = 0.011)]. LEP 19GG genotype carriers were found to have lower mineral bone density (MBD) of the femoral neck than heterozygotes (p = 0.06). In LEPR 223GlnArg heterozygotes, the mean MBD of the trochanter and whole hip was statistically significantly lower than that in patients with the genotype 223ArgArg (p = 0.013). 223GlnGln carriers were taller than 223GlnArg ones (p = 0.04). There were no associations of the clinical and biochemical parameters with the polymorphisms studied.
Conclusion. Our study confirmed the role of LEP A19G and LEPR Gln223Arg polymorphisms as important candidate genes involved in the formation of a predilection for OP.
Subjects and methods. PCR analysis was used to examine the polymorphisms among 428 women (254 patients with OP and 174 healthy women). The anthropometric, densitometric, and biochemical markers of bone remodeling and standard clinical and biochemical parameters were studied.
Results. Statistically significant differences were found in the distribution of the genotypes of LEP A19G polymorphism between the women with OP and the controls (χ2 = 9.41; p = 0.009). In the patients with OP, the 19GG genotype frequency was significantly higher than that in the controls [OR = 2.0; 95% confidence interval (CI) 1.13-3.52 (p = 0.011)]. LEP 19GG genotype carriers were found to have lower mineral bone density (MBD) of the femoral neck than heterozygotes (p = 0.06). In LEPR 223GlnArg heterozygotes, the mean MBD of the trochanter and whole hip was statistically significantly lower than that in patients with the genotype 223ArgArg (p = 0.013). 223GlnGln carriers were taller than 223GlnArg ones (p = 0.04). There were no associations of the clinical and biochemical parameters with the polymorphisms studied.
Conclusion. Our study confirmed the role of LEP A19G and LEPR Gln223Arg polymorphisms as important candidate genes involved in the formation of a predilection for OP.
About the Authors
Mikhail Yur'evich KrylovL I Benevolenskaya
V A Myakotkin
Mikhail Yuryevich Krylov
L I Benevolenskaya
V A Myakotkin
References
1. <div><p>Rosen C.J., Beamer W.G., Donahue L.R. et al. Defining the genetics of osteoporosis: Using the mouse to understand man. Osteoporosis Int 2001; 12: 803-10.</p><p>Uitterlinden A.G., van Meurs J.B., Rivadeneira F. et al. Identifying genetic risk factors for osteoporosis. J Musculoskelet Neuronal Interact 2006; 6: 16-6.</p><p>Tzakas P., Wong B.Y., Logan A.G. et al. Transforming growth factor beta-1 (TGFB1) and peak bone mass: Association between intragenic polymorphisms and quatitative ultrasound of the heel. BMC Musculoskelet Disord 2005; 14: 6-29.</p><p>Chung H.W., Seo J.-S., Hur S.E. et al. Association of interleukin-6 promoter variant with bone mineral density in premenopausal women. J Hum Genet 2003; 48: 243-8.</p><p>Grant S.F.A., Reid D.M., Blake G. et al. Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type 1-alpha 1 gene. Nat Genet 1996; 14: 203-5.</p><p>Uitterlinden A.G., Burger H., Huang Q. et al. Relation of alleles of the collagen type 1-alpha-1 gene virto bone density and the risk of osteoporotic fractures in postmenopausal women. N Engl J Med 1998; 338: 1016-21.</p><p>Baker A.R., McDonnell D.P., Hughes M. et al. Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci USA 1988; 85: 3294-8.</p><p>Тагиева А.Н., Сметник В.П., Сухих Г.Т. и др. Изучение роли генов рецептора витамина D (VDR), альфа-рецептора эстрогенов (ERα) и альфа-1-цепи коллагена первого типа (COLIA1) в заболеваемости постменопаузальным остеопорозом. Мед. генет. 2005; 4(2): 90-5.</p><p>Uitterlinden A.G., Arp P.P., Paeper B.W. et al. Polymorphisms in the sclerosteosis / van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites. Am J Hum Genet 2004; 75: 1032-45.</p><p>Mizuguchi T., Furuta I., Watanabe Y. et al. LRP5, low-density-lipoprotein-receptor- related protein 5, is a determinant for bone mineral density. J Hum Genet 2004; 49: 80-6.</p><p>Choi J.Y., Shin A., Park S.K. et al. Genetic polymorphisms OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women. Calcif Tissue Int 2005; 77: 152-9.</p><p>Крылов М.Ю., Греченко А.В., Самаркина Е.Ю. и др. Ассоциация минеральной плотности костной ткани с полиморфизмами гена альфа-рецептора эстрогена (ESR) при постменопаузальном остеопорозе. Науч.-практич. ревматол. 2005; 1: 8-11.</p><p>Ralston S.H. Genetic determinants of osteoporosis. Curr Opin Rheumatol 2005; 17: 475-9.</p><p>Ferrari S.L., Rizzoli R. Gene variants for osteoporosis and their pleiotropic effects in aging. Mol Aspects Med 2005; 26: 145-67.</p><p>Zhang Y., Proenca R., Maffei M. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-32.</p><p>Pasco J.A., Henry M.J., Kotowicz M.A. et al. Serum leptin levels are associated with bone mass in no obese women. J Clin Endocrinol Metab 2001; 86: 1884-7.</p><p>Blain H., Vuillemin A., Guillemin F. et al. Seruml leptin level is a predictor of bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2002; 87: 1030-5.</p><p>Isse N., Ogawa Y., Tamura N. et al. Structural organization and chromosomal assignment of the human obese gene. J Biol Chem 1995; 270: 27728-33.</p><p>Mammes O., Betoulle D., Aubert R. et al. Novel polymorphism in the 5' region of LEP gene. Diabetes 1998; 47: 487-9.</p><p>Hager J., Clement K., Francke S. et al. A polymorphism in the 5' untranslated region of the human ob gene is associated with low leptin levels. Int J Obes 1998; 22: 200-5.</p><p>Lucantoni R., Ponti E., Berselli M.E. et al. The A19G Polymorphism in the 5' Untranslated Region of the Human Obese GeneDoes Not Affect Leptin Levels in Severely Obese Patients. J Clin Endocrinol Metab 2000; 85: 3589-91.</p><p>Karvonen K., Pesonen U., Heinonen P. et al. Identification of new sequence variant in the leptin gene. J Clin Endocrinol Metab 1998; 83: 3239-42.</p><p>Perusse L., Rankinen T., Zuberi A. et al. The human obesity gene map: The 2004 update. Obes Res 2005; 13: 381-490.</p><p>Van der Vleuten G.M., Kluijtmans L.A., Hijmans A. et al. The Gln223Arg polymorphism in the leptin receptor is associated with familial combined hyperlipidemia. Int J Obes Relat Metab Disord 2006; 30: 892-8.</p><p>Park K.S., Shin H.D., Park B.L. et al. Polymorphisms in the leptin receptor (LEPR) - putative association with obesity and T2DM. J Hum Genet 2006; 51: 85-91.</p><p>Snoussi K., Strosberg A.D., Bouaouina N. et al. Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma. BMC Cancer 2006; 20: 6-38.</p><p>Zhang Y.Y., Gottardo L., Mlynarski W. et al. Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels. Atherosclerosis 2007; 191(1): 121-7.</p><p>Koh J.M., Kim D.J., Hong J.S. et al. Estrogen receptor alpha gene polymorphisms Pvu II and XbaI influence association between leptin receptor gene polymorphism (Gln223Arg) and bone mineral density in young men. Eur J Endocrinol 2002; 147: 777-83.</p><p>Song K.H., Koh J.M., Hong J.S. et al. Lack of association between bone mineral density and leptin receptor gene polymorphism in young women and postmenopausal women. Kor J Bone Metab 2003; 10: 39-46.</p><p>Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 12-5.</p><p>Grodin J., Siiteri P., McDonald P. Source of estrogen production in postmenopausal women. J Clin Endocrinol Metab 1973; 36: 207-14.</p><p>Reid I. Relationships among body mass, its components, and bone. Bone 2002; 13: 547-55.</p><p>Justensen J., Stenderup K., Ebbesen E.N. et al. Adipocyte tissue volum in bone marrow in increased with aging and in patients with osteoporosis. Biogerontology 2001; 2: 165-71.</p><p>Fairbrother U., Tanko L., Walley A. et al. Leptin Receptor Genotype at Gln223Arg Is Associated With Body Composition, BMD, and Vertebral Fracture in Postmenopausal Danish Women. J Bone Miner Res 2007; 22: 544-50.</p><p>Jiao J., Meng X.W., Xing X.P. et al. Bone mineral density and leptin receptor polymorphism Gln223Arg in Han women in Beijing. Zhong-hua Nei Ke Za Zhi 2004; 4: 276-9.</p><p>Crabbe P., Goemaere S., Zmierczak H. et al. Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men? Eur J Endocrinol 2006; 154: 707-14.</p><p>Rosen C.J., Ackert-Bicknell C., Beamer W.G. et al. Allelic differences in a quantitative trait locus affecting insulin-like growth factor-1 impact skeletal acquisition and body composition. Pediatr Nephrol 2005; 20: 255-60.</p></div><br />
Review
For citations:
Krylov M.Yu., Benevolenskaya L.I., Myakotkin V.A., Krylov M.Yu., Benevolenskaya L.I., Myakotkin V.A. LEPTIN A19G POLYMORPHISM AND LEPTIN RECEPTOR Gln223Arg AND Lys109Arg POLYMORPHISMSIN POSTMENOPAUSAL OSTEOPOROSIS. Rheumatology Science and Practice. 2010;48(5):27-31. (In Russ.) https://doi.org/10.14412/1995-4484-2010-727
Views:
1327
Email this article 