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American Journal of Biochemistry and Molecular Biology

Year: 2013 | Volume: 3 | Issue: 1 | Page No.: 159-166
Research Article

Tetranucleotide Repeat Polymorphism in the 3' UTR of the Human Leptin Gene and Risk of Type 2 Diabetes Mellitus in a South Indian Population

Kamakshi Chaithri Ponnaluri
Department of Genetics, Osmania University, Hyderabad-500007, Andhra Pradesh, India
LiveDNA: 91.12972
Parimala Narne
Department of Genetics, Osmania University, Hyderabad-500007, Andhra Pradesh, India
Mohd. Siraj
Department of Medicine, Deccan College of Medical Sciences, Hyderabad-500058, Andhra Pradesh, India
Mohd. Ishaq
Department of Genetics, Osmania University, Hyderabad-500007, Andhra Pradesh, India
Type 2 Diabetes Mellitus (T2DM), an increasingly common serious metabolic disorder has obesity as one of its major predisposing factors. Accumulating evidence suggests that the adipocyte-derived multifunctional hormone, leptin, may play a vital role in the modulation of obesity and subsequent T2DM. The association of polymorphic tetranucleotide repeat (TTTC)n polymorphism in the 3' UTR of the human Leptin gene (LEP-tet) with T2DM was examined in the present study. The study population comprised of 481 subjects including 305 patients and 176 controls. Genotyping of the polymorphic variant was carried out by PCR followed by agarose gel electrophoresis. The alleles of the polymorphism consisted of two groups with different size distributions: the shorter group (class I) and the longer group (class II). Analysis of allele frequencies and genotype frequencies between T2DM subjects and healthy controls revealed no significant differences. Risk estimates for different combinations of the LEP-tet genotypes showed that the I/II genotype was associated with modest 1.46 fold increased risk of T2DM (p = 0.04; 95% CI = 1.01-2.12). A similar trend could not be observed after stratification of the subjects based on sex or obesity. The results obtained in the present study indicated an insignificant influence of the leptin tetranucleotide repeat polymorphism on the development of T2DM. Further studies on a similar aspect would help clarify the issue.
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How to cite this article

Kamakshi Chaithri Ponnaluri, Parimala Narne, Mohd. Siraj and Mohd. Ishaq, 2013. Tetranucleotide Repeat Polymorphism in the 3' UTR of the Human Leptin Gene and Risk of Type 2 Diabetes Mellitus in a South Indian Population. American Journal of Biochemistry and Molecular Biology, 3: 159-166.

DOI: 10.3923/ajbmb.2013.159.166

URL: https://scialert.net/abstract/?doi=ajbmb.2013.159.166

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References

  1. Assal, H.S., M. Fath-Allah and A. Elsherbiny, 2007. Serum leptin and adiponectin in obese diabetic and non-diabetic. J. Med. Sci., 7: 865-869.
    CrossRefDirect Link
  2. Boden, G., X. Chen, J.W. Kolaczynski and M. Polansky, 1997. Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects. J. Clin. Invest., 100: 1107-1113.
    CrossRefPubMedDirect Link
  3. Chinookoswong, N., J.L. Wang and Z.Q. Shi, 1999. Leptin restores euglycemia and normalizes glucose turnover in insulin-deficient diabetes in the rat. Diabetes, 48: 1487-1492.
    CrossRefPubMedDirect Link
  4. Cook, K.S., H.Y. Min, D. Johnson, R.J. Chaplinsky, J.S. Flier, C.R. Hunt and B.M. Spiegelman, 1987. Adipsin: A circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science, 237: 402-405.
    CrossRefPubMedDirect Link
  5. Daimon, M., T. Oizumi, T. Saitoh, W. Kameda and H. Yamaguchi et al., 2002. Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese. Diabetes Res. Clin. Pract., 56: 147-152.
    CrossRefPubMedDirect Link
  6. Dehwah, M.A.S., Z. Shuang and Q.Y. Huang, 2008. The association between ACE gene I/D polymorphism and type 2 diabetes in han Chinese in hubei. Int. J. Osteoporosis Metabolic Disorders, 1: 1-7.
    CrossRefDirect Link
  7. Dehwah, M.A.S., Z. Shuang, W. Yan, P. Chan and Q.Y. Huang, 2008. Type 2 diabetes in han chinese in hubei. J. Applied Sci., 8: 1235-1241.
    CrossRefDirect Link
  8. Dehwah, M.A.S., Z. Shuang, W.Z. Hua, W. Min and Q.Y. Huang, 2009. Type 2 diabetes: Genetic advance and aetiology. J. Applied Sci., 9: 3407-3423.
    CrossRefDirect Link
  9. Dhanapal, K., N. Selvan and V. Dhananjeyan, 2010. A study on catalase activity and its genetic polymorphism in diabetes mellitus patients. J. Biol. Sci., 10: 653-657.
    CrossRefDirect Link
  10. Abd El-Ghaffar, N. and N.H. El-Said,, 2006. Hypoadiponectinaemia in Egyptian patients with type II diabetes mellitus with vascular complications. J. Med. Sci., 6: 626-630.
    CrossRefDirect Link
  11. Hegele, R.A., S.B. Harris, B. Zinman, A.J.G. Hanley and H. Cao, 2001. Absence of association of type 2 diabetes with CAPN10 and PC-1 polymorphisms in Oji-Cree. Diabetes Care, 24: 1498-1499.
    CrossRefPubMedDirect Link
  12. Horikawa, Y., N. Oda, N.J. Cox, X. Li and M. Orho-Melander et al., 2000. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat. Genet., 26: 163-175.
    Direct Link
  13. Ingalls, A.M., M.M. Dickie and G.D. Snell, 1996. Obese, a new mutation in the house mouse. Obes. Res., 4: 101-101.
    CrossRefPubMedDirect Link
  14. Isse, N., Y. Ogawa, N. Tamura, H. Masuzaki and K. Mori et al., 1995. Structural organization and chromosomal assignment of the human obese gene. J. Biol. Chem., 270: 27728-27733.
    CrossRefDirect Link
  15. King, H., R.E. Aubert and W.H. Herman, 1998. Global burden of diabetes, 1995-2025: Prevalence, numerical estimates and projections. Diabetes Care, 21: 1414-1431.
    CrossRefPubMedDirect Link
  16. Lahiri, D.K., S. Bye, J.I. Jr. Nurnberger, M.E. Hodes and M. Crisp, 1992. A non-organic and non-enzymatic extraction method gives higher yields of genomic DNA from whole-blood samples than do nine other methods tested. J. Biochem. Biophys. Meth., 25: 193-205.
    Direct Link
  17. Mohiti, J., F. Talebi and M. Afkhami-Ardekani, 2009. Circulation free leptin in diabetic patients and its correlation to insulin level. Pak. J. Biol. Sci., 12: 397-400.
    CrossRefPubMedDirect Link
  18. Montague, C.T., I.S. Farooqi, J.P. Whitehead, M.A. Soos and H. Rau et al., 1997. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature, 387: 903-908.
    CrossRefPubMedDirect Link
  19. Muzzin, P., R.C. Eisensmith, K.C. Copeland and S.L. Woo, 1996. Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. Proc. Natl. Acad. Sci., 93: 14804-14808.
    Direct Link
  20. Randle, P.J., P.B. Garland, C.N. Hales and E.A. Newsholme, 1963. The glucose fatty-acid cycle its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet, 281: 785-789.
    CrossRefDirect Link
  21. Scherer, P.E., S. Williams, M. Fogliano, G. Baldini and H.F. Lodish, 1995. A novel serum protein similar to C1q produced exclusively in adipocytes. J. Biol. Chem., 270: 26746-26749.
    Direct Link
  22. Segal, K.R., M. Landt and S. Klein, 1996. Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes, 45: 988-991.
    CrossRefPubMedDirect Link
  23. Shintani, M., H. Ikegami, E. Yamato, Y. Kawaguchi and T. Fujisawa et al., 1996. A novel microsatellite polymorphism in the human OB gene: A highly polymorphic marker for linkage analysis. Diabetologia, 39: 1398-1401.
    CrossRefDirect Link
  24. Sicree, R., J. Shaw and P. Zimmet, 2006. Diabetes and Impaired Glucose Tolerance. In: Prevalence and Projections, Gan, D. (Ed). 3rd Edn., International Diabetes Federation, Brussels, Belgium, ISBN-10: 2930229144, pp: 16-103.
  25. Sivitz, W.I., S.A. Walsh, D.A. Morgan, M.J. Thomas and W.G. Haynes, 1997. Effects of leptin on insulin sensitivity in normal rats. Endocrinology, 138: 3395-3401.
    CrossRefPubMedDirect Link
  26. Vasudevan, R., P. Ismail, J. Stanslas and N. Shamsudin, 2008. Association of G2350A polymorphism of angiotensin converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects. J. Biol. Sci., 8: 1045-1050.
    CrossRefDirect Link
  27. Zhang, Y., R. Proenca, M. Maffei, M. Barone, L. Leopold and J.M. Friedman, 1994. Positional cloning of the mouse obese gene and its human homologue. Nature, 372: 425-432.
    CrossRefDirect Link
  28. Zierath, J.R., E.U. Frevert, J.W. Ryder, P.O. Berggren and B.B. Kahn, 1998. Evidence against a direct effect of leptin on glucose transport in skeletal muscle and adipocytes. Diabetes, 47: 1-4.
    CrossRefPubMedDirect Link
  29. American Diabetes Association, 2009. Diagnosis and classification of diabetes mellitus. Diabetes Care, 32: S62-S67.
    CrossRefDirect Link

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