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The common pentanucleotide polymorphism of the 3’-untranslated region of the leptin receptor gene is associated with obesity in Saudi females

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DOI: 10.4236/health.2013.52038    2,677 Downloads   4,186 Views   Citations

ABSTRACT

Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. Leptin receptor (LEPR) gene has been intensively evaluated in the search of variants that could be related to obesity. The results of most of these studies have been controversial. We investigated the effects of leptin receptor gene 3’-untranslated region (3’-UTR) polymorphism on phenotype, metabolic parameters and anthropometric measurements of obese Saudi females. 122 healthy women aged 19 to 36 years. The subjects were divided into 3 groups according to their body mass index BMI; lean (BMI 18 - 24), overweight (BMI 25 - 29) and obese (BMI ≥ 30). There were 13 homozygotes and 34 heterozygotes for the 3’-UTR insertion allele amongst all 122 women. The results of this study show that the allele frequency of the insertion allele (I) of 3’UTR was significantly higher in overweight (35.3) and obese females (32.2) compared to the frequency in lean females (15.6). The insertion allele was associated with increased BMI in obese groups. The results obtained from this study indicated that in the obese subjects most variable values increased in I/I homozygote but the significant high value recorded among BMI (40.9 ± 7.11 kg/m2, P = 0.042). Our findings indicated that, the obesity in Saudi females is influenced by alteration in the leptin receptor gene 3’-UTR polymorphism.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Daghestani, M. , Daghestani, M. , Ozand, P. , Al-Himaidi, A. , Daghestani, M. , Aleisa, N. , Hakami, H. , Eldali, A. and Al-odaib, A. (2013) The common pentanucleotide polymorphism of the 3’-untranslated region of the leptin receptor gene is associated with obesity in Saudi females. Health, 5, 285-291. doi: 10.4236/health.2013.52038.

References

[1] Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L. and Friedman, J.M. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature, 372, 425-432. doi:10.1038/372425a0
[2] Campfield, L.A., Smith, F.J., Guisez, Y., Devos, R. and Burn, P. (1995) Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neutral networks. Science, 269, 546-549. doi:10.1126/science.7624778
[3] Pelleymounter, M.A., Cullen, M.J., Baker, M.B., Hecht, R., Winters, D., Boone, T. and Collins, F. (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science, 269, 540-543. doi:10.1126/science.7624776
[4] Frederich, R.C., Lollmann, B., Hamann, A., Napolitano Rosen, A., Kahn, B.B., Lowell, B.B. and Flie, J.S. (1995) Expression of ob mRNA and its encoded protein in rodents. Journal of Clinical Investigation, 96, 1658-1663. doi:10.1172/JCI118206
[5] Maffei, M., Halaas, J., Ravussin, E., Pratley, R.E., Lee, G.H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Rangana than, S., Kern, P.A. and Friedman, J.M. (1995) Leptin levels in human and rodent: Measurement of plasma lep tin and ob RNA in obese and weight-reduced subjects. Nature Medicine, 1, 1155-1161. doi:10.1038/nm1195-1155
[6] Considine, R.V., Sinha, M.K., Heiman, M.L., Kriauciunas, A., Stephens, T.W., Nyce, M.R., Ohannesian, J.P., Marco, C.C., McKee, L.J., Bauer, T.L. and Caro, J.F. (1996) Se rum immunoreactive-leptin concentrations in normal weight and obese humans. New England Journal of Me dicine, 334, 292-295. doi:10.1056/NEJM199602013340503
[7] Chung, W.K., Power-Kehoe, L., Chua, M., Chu, F., Aronne, L., Huma, Z., Sothern, M., Udall, J.N., Kahle, B. and Leibel, R.L. (1997) Exonic and intronic sequence varia tion in the human leptin receptor gene (LEPR). Diabetes, 46, 1509-1511.
[8] Guízar-Mendoza, J.M., Amador-Licona, N., Flores-Mar tínez, S.E., López-Cardona, M.G., Ahuatzin-Trémary, R. and Sánchez-Corona, J. (2005) Association analysis of the Gln223Arg polymorphism in the human leptin recap tor gene, and traits related to obesity in Mexican adoles cents. Journal of Human Hypertension, 19, 341-346. doi:10.1038/sj.jhh.1001824
[9] van der Vleuten, G.M., Kluijtmans, L.A., Hijmans, A., Blom, H.J., Stalenhoef, A.F. and de Graaf, J. (2006) The Gln223Arg polymorphism in the leptin receptor is asso ciated with familial combined hyperlipidemia. Interna tional Journal of Obesity (Lond), 30, 892-898.
[10] Friedman, J.M. and Halaas, J.L. (1998) Leptin and the re gulation of body weight in mammals. Nature, 395, 763 770. doi:10.1038/27376
[11] Montague, C.T., Farooqi, I.S., Whitehead, J.P., Soos, M.A., Rau, H., Wreham, N.J., Sewter, C.P., Digby, J.E., Mo hammed, S.N., Hurst, J.A., Cheetham, C.H., Early, A.R., Barnett, A.H., Prins, J.B. and O’Rahilly, S. (1997) Con genital leptin deficiency is associated with severe early onset obesity in humans. Nature, 387, 903-908. doi:10.1038/43185
[12] Wauters, M., Mertens, I., Chagnon, M., Rankinen, T., Considine, R.V., Chagnon, Y.C., Van Gaal, L.F. and Bou chard, C. (2001) Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women. International Journal of Obesity and Related Metabolic and Disorders, 25, 714-720. doi:10.1038/sj.ijo.0801609
[13] van Rossum, C.T., Hoebee, B., van Baak, M.A., Mars, M., Saris, W.H. and Seidell, J.C. (2003) Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults. Obesity and Research, 11, 377-386. doi:10.1038/oby.2003.51
[14] Wauters, M., Considine, R.V., Chagnon, M., et al. (2002) Leptin levels, leptin receptor gene polymorphisms, and energy metabolism in women. Obesity and Research, 10, 394-400. doi:10.1038/oby.2002.54
[15] de Luis Roman, D., de la Fuente, R.A., Sagrado, M.G., Izaola, O. and Vicente, R.C. (2006) Leptin receptor Lys656Asn polymorphism is associated with decreased leptin response and weight loss secondary to a lifestyle modification in obese patients. Archives of Medical Research, 37, 854-859. doi:10.1016/j.arcmed.2006.03.009
[16] Angel-Chávez, L.I., Tene-Pérez, C.E. and Castro, E. (2012) Leptin receptor gene K656N polymorphism is associated with low body fat levels and elevated high-density cholesterol levels in Mexican children and adolescents. En docrine Research, 37, 124-134.
[17] Wauters, M., Mertens, I., Rankinen, T., Chagnon, M., Bouchard, C. and VanGaal, L. (2001) Leptin receptor gene polymorphisms are associated with insulin in obese women with impaired glucose tolerance. Journal of Clinical Endocrinology & Metabolism, 86, 3227-3232. doi:10.1210/jc.86.7.3227
[18] Francke, S., Clement, K., Dina, C., Inoue, H., Behn, P., Vatin, V., Basdevant, A., Guy-Grand, B., Permutt, M.A., Froguel, P. and Hager, J. (1997) Genetic studies of the leptin receptor gene in morbidly obese French Caucasian families. Human Genetics, 100, 491-496. doi:10.1007/s004390050540
[19] Oksanen, L., Kaprio, J., Mustajoki, P. and Kontula, K.A. (1998) common pentanucleotide polymorphism of the 3’ untranslated part of the leptin receptor gene generates a putative stem-loop motif in the mRNA and is associated with serun insulin levels in obese individuals. Interna tional Journal of Obesity, 22, 634-640. doi:10.1038/sj.ijo.0800639
[20] WHO (1988) Measuring obesity: Classification and de scription of anthropometric data. Copehhagen, WHO, EUR/ ICP/NUT 125.
[21] Matsuoka, N., Ogawa, Y., Hosada, K., Matsuda, J., Ma suzaki, H., Miyawaki, T., Azuma, N.N., Natsui, K., Ni shimura, H., Yoshimasa, Y., Nishi, N., Thompson, D.B. and Nakao, K. (1997) Human leptin receptor gene in obese Japanese subjects: Evidence against either obe sity-causing mutations or association of sequence variants with obesity. Diabetologia, 40, 1204-1210. doi:10.1007/s001250050808
[22] Thompson, D.B., Ravussin, E., Bennett, P.H. and Bogar dus, C. (1997) Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indi ans. Human Molecular Genetics, 6, 675-679. doi:10.1093/hmg/6.5.675
[23] Quinton, N.D., Lee, A.J., Ross, R.J.M., Eastell, R. and Blakemore, A.I.F. (2001) A single nucleotide polymer phism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women. Human Genetics, 108, 233-236. doi:10.1007/s004390100468
[24] Heo, M., Leibel, R.L., Fontaine, K.R., Boyer, B.B., Chung, W.K., Koulu, M., Karvonen, M.K., Pesonen, U., Rissanen, A., Laakso, M., Uusitupa, M.I., Chagnon, Y., Bouchard, C., Donohoue, P.A., Burns, T.L., Shuldiner, A.R., Silver, K., Andersen, R.E.R.E., Pedersen, O., Echwald, S., So rensen, T.L., Behn, P., Permutt, M.A., Jacobs, K.B., Elston, R.C., Hoffman, D.J., Gropp, E. and Allison, D.B. (2002) A meta-analytic investigation of linkage and association of common leptin receptor (LEPR) polymorphisms with body mass index and waist circumference. International Journal of Obesity and Related Metabolic Disorders, 26, 640-646. doi:10.1038/sj.ijo.0801990
[25] Lakka, H.M., Oksanen, L., Tuomainen, T.P., Kontula, K. and Salonen, J.T. (2000) The common pentanucleotide polymorphism of the 3-untranslated region of the leptin receptor gene is associated with serum insulin level and the risk of type 2 diabetes in non-diabetic men, a pro spective case-control study. Journal of Internal Medicine, 248, 77-83. doi:10.1046/j.1365-2796.2000.00696.x
[26] Oswal, A. and Yeo, G. (2010) Leptin and the control of body weight: A review of its diverse central targets, sig naling mechanisms, and role in the pathogenesis of obesity. Obesity (Silver Spring), 18, 221-229. doi:10.1038/oby.2009.228
[27] Huang, H., Kong, D., Byun, K.H., Ye, C., Koda, S., Lee, D.H., Oh, B.C., Lee, S.W., Lee, B., Zabolotny, J.M., Kim, M.S., Bj?rb?k, C., Lowell, B.B. and Kim, Y.B. (2012) Rho-kinase regulates energy balance by targeting hypo thalamic leptin receptor signaling. Nature Neuroscience, 15, 1391-1398. doi:10.1038/nn.3207
[28] Velloso, L.A. and Schwartz, M.W. (2011) Altered hypo thalamic function in diet-induced obesity. International Journal of Obesity (Lond), 35, 1455-1465. doi:10.1038/ijo.2011.56
[29] Zacharova, J., Todorova, B.R., Chiasson, J.L. and Laakso, M. (2005) The G-250A substitution in the promoter region of the hepatic lipase gene is associated with the con version from impaired glucose tolerance to type 2 diabetes: The STOP-NIDDM trial. Journal of Internal Medicine, 257, 185-193. doi:10.1111/j.1365-2796.2004.01435.x
[30] Nannipieri, M., Posadas, R., Williams, K., Politi, E., Gonzales-Villalpando, C., Stern, M.P. and Ferrannini, E. (2003) Association between polymorphisms of the atrial natriuretic peptide gene and proteinuria: A population based study. Diabetologia, 46, 429-432.
[31] Ross, J. (1995) mRNA stability in mammalian cells. Microbiological Review, 59, 423-450.
[32] Brown, C.Y., Lagnado, C.A. and Goodall, G.J. (1996) A cytokine mRNA-destabilizing element that is structurally and functionally distinct from A + U-rich elements. Proceedings of the National Academy Sciences USA, 93, 13721 13725.

  
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