Biopolym. Cell. 2015; 31(1):34-37.
Biomedicine
Association of the leukemia inhibitory factor gene polymorphism rs929271 with idiopathic mild intellectual disability
1, 2Gulkovskyi R. V., 2Volkova L. S., 2Livshits L. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Educational and Scientific Center "Institute of Biology",
    Taras Shevchenko National University of Kyiv
    64/13, Volodymyrska Str., Kyiv, Ukraine, 01601

Abstract

Aim. To investigate the possible association of LIF gene polymorphism rs929271 with mild intellectual disability (ID). Methods. The group of patients with mild (IQ score between 50 and 70) idiopathic intellectual disability consisted of 64 individuals including 40 (62.5 %) males and 24 (47.5 %) females. The control group consisted of 238 healthy volunteers from different regions of Ukraine. Polymorphic variants of LIF gene rs929271 were detected using PCR followed by Hinf1 RFLP analysis. Results. The data concerning LIF genotypes and allelic variants distribution in ID patients and control group were obtained. Statistical analysis shows significant differences at rs929271 for both genotype and allele frequency when comparing ID cases and controls (p = 0.01 and 0.02, respectively). Conclusions. Our results suggest that LIF gene polymorphism rs929271 is associated with idiopathic mild intellectual disability. Therefore, we propose LIF as a new marker of genetic susceptibility for intellectual disability.
Keywords: LIF gene, intellectual disability, polymorphism, population

References

[1] Leonard H, Wen X. The epidemiology of mental retardation: challenges and opportunities in the new millennium. Ment Retard Dev Disabil Res Rev. 2002;8(3):117-34.
[2] Flint J. Genetic basis of cognitive disability. Dialogues Clin Neurosci. 2001;3(1):37-46.
[3] Holmberg KH, Patterson PH. Leukemia inhibitory factor is a key regulator of astrocytic, microglial and neuronal responses in a low-dose pilocarpine injury model. Brain Res. 2006;1075(1):26-35.
[4] Kerr BJ, Patterson PH. Leukemia inhibitory factor promotes oligodendrocyte survival after spinal cord injury. Glia. 2005;51(1):73–9.
[5] Sugiura S, Lahav R, Han J, Kou SY, Banner LR, de Pablo F, Patterson PH. Leukaemia inhibitory factor is required for normal inflammatory responses to in­jury in the peripheral and central nervous systems in vi­vo and is chemotactic for macrophages in vitro. Eur J Neu­rosci. 2000; 12(2):457–66.
[6] Barres BA, Schmid R, Sendnter M, Raff MC. Multiple extracellular signals are required for long-term oligodendrocyte survival. Development. 1993;118(1):283-95.
[7] Martinou JC, Martinou I, Kato AC. Cholinergic differentiation factor (CDF/LIF) promotes survival of isolated rat embryonic motoneurons in vitro. Neuron. 1992;8(4):737-44.
[8] Niwa H, Ogawa K, Shimosato D, Adachi K. A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells. Nature. 2009;460(7251):118-22.
[9] Hirai H, Karian P, Kikyo N. Regulation of embryonic stem cell self-renewal and pluripotency by leukaemia inhibitory factor. Biochem J. 2011;438(1):11-23.
[10] Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell. 2002;110(4):443-55.
[11] Thomas GM, Huganir RL. MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci. 2004;5(3):173-83.
[12] Hamdan FF, Gauthier J, Spiegelman D, Noreau A, Yang Y, Pellerin S, Dobrzeniecka S, C?t? M, Perreau-Linck E, Carmant L, D'Anjou G, Fombonne E, Addington AM, Rapoport JL, Delisi LE, Krebs MO, Mouaffak F, Joober R, Mottron L, Drapeau P, Marineau C, Lafreni?re RG, Lacaille JC, Rouleau GA, Michaud JL; Synapse to Disease Group. Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation. N Engl J Med. 2009;360(6):599-605.
[13] Hamdan FF, Daoud H, Piton A, Gauthier J, Dobrzeniecka S, Krebs MO, Joober R, Lacaille JC, Nadeau A, Milunsky JM, Wang Z, Carmant L, Mottron L, Beauchamp MH, Rouleau GA, Michaud JL. De novo SYNGAP1 mutations in nonsyndromic intellectual disability and autism. Biol Psychiatry. 2011;69(9):898-901.
[14] Krepischi AC, Rosenberg C, Costa SS, Crolla JA, Huang S, Vianna-Morgante AM. A novel de novo microdeletion spanning the SYNGAP1 gene on the short arm of chromosome 6 associated with mental retardation. Am J Med Genet A. 2010;152A(9):2376-8.
[15] Delaunoy JP, Dubos A, Marques Pereira P, Hanauer A. Identification of novel mutations in the RSK2 gene (RPS6KA3) in patients with Coffin-Lowry syndrome. Clin Genet. 2006;70(2):161-6.
[16] Field M, Tarpey P, Boyle J, Edkins S, Goodship J, Luo Y, Moon J, Teague J, Stratton MR, Futreal PA, Wooster R, Raymond FL, Turner G. Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and nonsyndromic X-linked mental retardation. Clin Genet. 2006;70(6):509-15.
[17] Sutherland GR, Baker E, Hyland VJ, Callen DF, Stahl J, Gough NM. The gene for human leukemia inhibitory factor (LIF) maps to 22q12. Leukemia. 1989;3(1):9-13.
[18] Ishida R, Ezura Y, Iwasaki H, Nakazawa I, Kajita M, Kodaira M, Ito H, Emi M. Linkage disequilibrium and haplotype analysis among four novel single-nucleotide polymorphisms in the human leukemia inhibitory factor (LIF) gene. J Hum Genet. 2001;46(10):557-9.
[19] Okahisa Y, Ujike H, Kunugi H, Ishihara T, Kodama M, Takaki M, Kotaka T, Kuroda S. Leukemia inhibitory factor gene is associated with schizophrenia and working memory function. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(1):172-6.
[20] Kim Y, Park J, Lee C. Multilocus genotypic association with vascular dementia by multifactor dimensionality reducti­on and entropy-based estimation. Psychiatr Genet. 2009;19(5): 253–8.
[21] Cordell HJ, Clayton DG. Genetic association studies. Lancet. 2005 Sep 24-30;366(9491):1121-31.
[22] Balding DJ. A tutorial on statistical methods for population association studies. Nat Rev Genet. 2006;7(10):781-91.
[23] Sullivan KM, Dean A, Soe MM. OpenEpi: a web-based epidemiologic and statistical calculator for public health. Public Health Rep. 2009;124(3):471-4.