Skip to main content
SpringerLink
Log in

Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus

  • Published:
Genes & Nutrition Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate possible associations of -2548 G/A polymorphism in leptin gene promoter and pregnancy-associated diseases with abnormal fetal growth such as preeclampsia and gestational diabetes. The study was also focused on whether it is rather maternal or fetal variants that determines the pathological growth status. Peripheral or cord blood samples obtained from 49 preeclamptic women and their 39 newborns, 53 healthy controls and their 53 healthy newborns and 48 patients with gestational diabetes mellitus were evaluated for leptin gene (LEP) locus -2548 genotypes. The significantly higher risk for gestational diabetes mellitus was observed in the presence of an allele (AA and AG genotypes) against carriers of GGgenotype(OR=2.84, 95%CI1.14–7.07,p=0.02). Thereisa significant risk of diabetes mellitus associated to A allele (OR=1.79, 95%CI 1.02–3.14, p=0.03). Furthermore, evaluations of preeclamptic patients’ data revealed a significant association of genotype distribution and delivery and spontaneous abortion rate, where the GG carriers performed the highest pregnancy rate while the AG carriers performed the lowest spontaneous abortion rate. Our results support the hypothesis for -2548 G/A leptin gene polymorphism involvement in ethiopathogenesis of pregnancy-associated diseases with abnormal fetal growth, especially gestational diabetes mellitus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baumann, H., Morella, K.K., White, D.W., Dembski, M., Bailon, P.S., Kim, H., Lai, C.F. and Tartaglia, L.A. (1996) The full-length leptin receptor has signaling capabilities of interleukin 6-type receptors.Proceedings of the National Academy of Sciences of the United States of America 16:8374–8

    Article  Google Scholar 

  • Bi, S., Gavrilova, O. and Gong, D.W. (1997) Identification of a placental enhancer for the human leptin gene.The Journal of biological chemistry 48:30583–8.

    Article  Google Scholar 

  • 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 neural networks.Science 269:546–9

    Article  PubMed  CAS  Google Scholar 

  • Clement, K., Garner, C., Hager, J., Philippi, A., LeDuc, C., Carey, A., Harris, T.J., Jury C., Cardon L.R., Basdevant, A., Démenais, F., Guy-Grand, B., North, M. and Froguel, P. (1996) Indication for linkage of the human OB gene region with extreme obesity.Diabetes 5:687–90

    Article  Google Scholar 

  • Dornhorst, A., Paterson, C.M., Nicholls, J.S., Wadsworth, J., Chiu, D.C., Elkeles, R.S., Johnston, D.G. and Beard, R.W. (1992) High prevalence of gestational diabetes in women from ethnic minority groups.Diabetic Medicine 9:820–5

    Article  PubMed  CAS  Google Scholar 

  • Festa, A., Shnawa, N, Krugluger, W., Hopmeier, P., Schernthaner, G. and Haffner, S.M. (1999) Relative hypoleptinaemia in women with mild gestational diabetes mellitus.Diabetic Medicine 8:656–62.

    Article  Google Scholar 

  • Fox, C., Esparza, J., Nicolson, M., Bennett, P.H., Schulz, L.O. and Valencia, M.E. (1999). Plasmaleptin concentrations in Pima Indians living in drastically different environments.Diabetes Care 3:413–7.

    Article  Google Scholar 

  • Golden, PL., Maccagnan, TJ. and Pardridge, W.M. (1997) Human blood-barrier leptin receptor; binding and endocytosis in isolated human brain microvessels.Journal of Clinical Investigation 1:14–8

    Google Scholar 

  • Green, E.D., Maffei, M. and Braden, V.V. (1995) The human obese (Ob) gene — RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome.Genome Research 1:5–12

    Article  Google Scholar 

  • Grosfeld, A., Turban, S., Andre, J., Cauzac, M., Challier, J.C., Hauguel-de Mouzon, S., Guerre-Millo, M. (2001) Transcriptional effect of hypoxia on placental leptin.Federation of European Biochemical Societies Letters 3:122–6.

    Google Scholar 

  • Halaas, J.L., Gajiwala, K.S., Maffei, M., Cohen, S.L., Chait, B.T., Rabinowitz, D., Lallone, R.L., Burley S.K. and Friedman, J.M. (1995) Weight-reducing effects of the plasma protein encoded by the obese gene.Science 269:543–6

    Article  PubMed  CAS  Google Scholar 

  • Hamajima, N., Saito, T, Matsuo, K., Suzuki, T., Nakamura, T., Matsuura, A., Okuma, K. and Tajima, K. (2002) Genotype frequencies of 50 polymorphisms for 241 Japanese non-cancer patients.Journal of epidemiology 3:229–36.

    Google Scholar 

  • Henson, M.C. and Castracane, V.D. (2000) Leptin in pregnancy.Biology ofreproduction 5:1219–28

    Article  Google Scholar 

  • Hoffman, L., Nolan, C., Wilson, J.D., Oats, J.J. and Simmons, D. (1998) Gestational diabetes mellitus—management guidelines — The Australasian Diabetes in Pregnancy Society.The Medical journal of Australia 2:93–7.

    Google Scholar 

  • Hoffstedt, J., Eriksson, P., Mottagui-Tabar, S. and Arner, P. (2002) A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin.Hormone and metabolic research 7:355–9

    Article  Google Scholar 

  • Holness, M.J., Munns, M.J. and Sugden, M.C. (1999) Current concepts concerning the role of leptin in reproductive function.Molecular and cellular endocrinology 1–2:11–20.

    Article  Google Scholar 

  • Jaquet, D., Leger, J., Levy-Marchal, C., Oury J.F. and Czernichow, P. (1998) Ontogeny of leptin in human fetuses and newborns: effect of intrauterine growth retardation on serum leptin concentrations.The Journal of clinical endocrinology and metabolism 4:1243–6.

    Article  Google Scholar 

  • Lea, R.G., Howe, D., Hannah, L.T., Bonneau, O., Hunter, L. and Hoggard, N. (2000) Placental leptin in normal, diabetic and fetal growth-retarded pregnancies.Molecular human reproduction 8:763–9.

    Article  Google Scholar 

  • Lepercq, J., Cauzac, M., Lahlou, N., Timsit, J., Girard, J., Auwerx, J. and Hauguel-de Mouzon, S. (1998) Over expression of placental leptin in diabetic pregnancy: a critical role for insulin.Diabetes 5:847–50.

    Article  Google Scholar 

  • Li, W.D., Reed, D.R., Lee, J.H., Xu, W., Kilker, R.L., Sodam, B.R. and Price, R.A. (1999) Sequence variants in the 5′ flanking region of the leptin gene are associated with obesity in women.Annals of human genetics Pt 3:227–34

    Article  Google Scholar 

  • Malmstrom, R., Taskinen, M.R., Karonen, S.L. and Yki-Jarvinen, H. (1996) Insulin increases plasma leptin concentrations in normal subjects and patients with NIDDM.Diabetologia 8:993–6.

    Article  Google Scholar 

  • Mamma, O., Betoulle, D., Aubert, R., Herbeth, B., Siest, G. and Fumeron, F. (2000) Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight.Annals of human genetics 5:391–4.

    Google Scholar 

  • Masuzaki, H., Ogawa, Y. and Sagawa, N. (1997) Non-adipose tissue production of leptin: Leptin as a novel placenta-derived hormone in humans.Nature Medicine 9:l029–33

    Google Scholar 

  • Meissner, U., Ostreicher, I., Allabauer, I., Rascher, W. and Dotsch, J. (2003) Synergistic effects of hypoxia and insulin are regulated by different transcriptional elements of the human leptin promoter.Biochemical and biophysical research communications 2:707–12

    Article  CAS  Google Scholar 

  • Nieters, A., Becker, N. and Linseisen, J. (2002) Polymorphisms in candidate obesity genes and their interaction with dietary intake of n-6 polyunsaturated fatty acids affect obesity risk in a sub-sample of the EPIC-Heidelberg cohort.European journal of nutrition 5:210–21

    Article  CAS  Google Scholar 

  • Pelleymounter, M.A., Cullen, M.J., Baker, M.B., Hecht, R., Winters, D., Boone, T. and Collins, F (1995). Effect of the obese gene product on body weight regulation in ob/ob mice.Science 269:540–3

    Article  PubMed  CAS  Google Scholar 

  • Simmons, D., Breier, B.H. (2002) Fetal overnutrition in Polynesian pregnancies and in gestational diabetes may lead to dysregulation of the adipoinsular axis in offspring.Diabetes Care 9:1539–44

    Article  Google Scholar 

  • Stephens, T.W., Basinski, M., Bristow, P.K., Bue-Valleskey, J.M., Burgett, S.G. and Craft, L. (1995) The role of neuropeptide Yin the antiobesity action of the obese gene product.Nature 377:530–2

    Article  PubMed  CAS  Google Scholar 

  • Utriainen, T., Malmstrom, R., Makimattila, S. and Yki-Jarvinen, H. (1996) Supraphysiological hyperinsulinemia increases plasma leptin concentrations after 4 h in normal subjects.Diabetes 10:1364–6.

    Article  Google Scholar 

  • Weigle, D.S., Bukowski, T.R., Foster, D.C., Holderman, S., Kramer, J.M. and Lasser, G. (1995) Recombinant ob protein reduces feeding and body weight in the ob/ob mouse.Journal of Clinical Investigation 4:2065–70.

    Article  Google Scholar 

  • 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 372:425–32

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathological Physiology, Faculty of Medicine, Masaryk University, 662 43, Brno, Czech Republic

    Julie Anna Bienertová Vaškú, Anna Vaškú & Petr Bienert

  2. Clinic of Obstetrics and Gynecology, Masaryk University affiliated Hospital, 602 00, Brno, Czech Republic

    Zuzana Dostálová

Authors
  1. Julie Anna Bienertová Vaškú
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Vaškú
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zuzana Dostálová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Petr Bienert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julie Anna Bienertová Vaškú.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vaškú, J.A.B., Vaškú, A., Dostálová, Z. et al. Association of leptin genetic polymorphism -2548 G/A with gestational diabetes mellitus. Genes Nutr 1, 117–123 (2006). https://doi.org/10.1007/BF02829953

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02829953

Key Words

Search

Navigation