Klotho gene polymorphism -395 G
More details
Hide details
Department of Pneumonology, Medical School of Alexandroupolis Democritus University of Thrace
Department of Endocrinology, Medical School of Alexandroupolis Democritus University of Thrace
Genetics Unit, Medical School, University of Ioannina, Greece
Publication date: 2021-07-26
Corresponding author
Ioannis Sotiriou   

Department of Pneumonology University Hospital of Alexandroupolis 68100 Alexandroupolis, Greece
Pneumon 2010;23(4):348-354
The function of the Klotho gene, originally identified by insertional mutagenesis in mice, is to suppress multiple aging phenotypes. It has been shown that a mutant Klotho gene is associated with pulmonary emphysema in mice. The aims of this study were to detect Klotho gene polymorphisms (-395G>A SNP) and to identify their possible relationships with clinical findings in patients with chronic obstructive pulmonary disease (COPD).

In 167 patients with COPD -395G>A SNP of the Klotho gene was genotyped by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) coupled with sequencing. The possible relationship was explored of -395G>A SNP with clinical findings such as lung function parameters, staging according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and body mass index (BMI).

Of the 167patients with COPD, 99 (59.3%) presented the wild type -395G allele, 62 (37.1%) were heterozygotes (–395GA allele), and 6 (3.6%) presented the non-wild type–395A allele. In these COPD patients there was an association between Klotho genotypes and BMI (p=0.025). No association was found between Klotho gene polymorphism and disease severity, assessed by spirometry, arterial blood gases and GOLD stage.

Klotho -395G>A polymorphisms are detected in patients with COPD and are associated with BMI, but not with various parameters of disease severity. This may suggest a possible metabolic pathway in the implication of Klotho deficient gene in the pathophysiology of emphysema in COPD patients.

Hoyert DL, Heron MP, Murphy SL, Kung HC. Deaths: final data for 2003. Natl Vital Stat Rep 2006;54(13):1-120.
Ezzati M, Lopez AD. Estimates of global mortality attributable to smoking in 2000. Lancet 2003;362(9387):847-52.
Celli BR, MacNee W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23(6):932-46.
Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med 2000;343(4):269-80.
Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 2003;22(4):672-88.
Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390(6655):45-51.
Matsumura Y, Aizawa H, Shiraki-Iida T, et al. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun 1998;242(3):626-30.
Hayashi Y, Okino N, Kakuta Y, et al. Klotho-related protein is a novel cytosolic neutral beta -glycosylceramidase. J Biol Chem 2007;282:30889-900.
Kawano K, Ogata N, Chiano M, et al. Klotho gene polymorphisms associated with bone density of aged postmenopausal women. J Bone Miner Res 2002;17(10):1744-51.
Suga T, Kurabayashi M, Sando Y, et al. Disruption of the klotho gene causes pulmonary emphysema in mice. Defect in maintenance of pulmonary integrity during postnatal life. Am J Respir Cell Mol Biol 2000;22(1):26-33.
Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med 2001;163(5):1256-76.
Landbo C, Prescott E, Lange P, Vestbo J, Almdal TP. Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999;160(6):1856-61.
Funada Y, Nishimura Y, Yokoyama M. Imbalance of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 is associated with pulmonary emphysema in Klotho mice. Kobe J Med Sci 2004;50(3-4):59-67.
Minematsu N, Nakamura H, Tateno H, Nakajima T, Yamaguchi K. Genetic polymorphism in matrix metalloproteinase-9 and pulmonary emphysema. Biochem Biophys Res Commun 2001;289(1):116-9.
Hirano K, Sakamoto T, Uchida Y, et al. Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease. Eur Respir J 2001;18(5):748-52.
Ogata N, Matsumura Y, Shiraki M, et al. Association of klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women. Bone 2002;31(1):37- 42.
Kim Y, Kim JH, Nam YJ, et al. Klotho is a genetic risk factor for ischemic stroke caused by cardioembolism in Korean females. Neurosci Lett 2006;407(3):189-94.
Deary IJ, Harris SE, Fox HC, et al. KLOTHO genotype and cognitive ability in childhood and old age in the same individuals. Neurosci Lett 2005;378(1):22-7.
Arking DE, Krebsova A, Macek M, Sr., et al. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A 2002;99(2):856-61.
Tzanakis N, Anagnostopoulou U, Filaditaki V, Christaki P, Siafakas N. Prevalence of COPD in Greece. Chest 2004;125(3):892- 900.
Imamura A, Okumura K, Ogawa Y, et al. Klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese. Clin Chim Acta 2006;371(1-2):66-70.
Shimoyama Y, Nishio K, Hamajima N, Niwa T. KLOTHO gene polymorphisms G-395A and C1818T are associated with lipid and glucose metabolism, bone mineral density and systolic blood pressure in Japanese healthy subjects. Clin Chim Acta 2009;406(1-2):134-8.
Saito Y, Nakamura T, Ohyama Y, et al. In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome. Biochem Biophys Res Commun 2000;276(2):767- 72.
Saito Y, Yamagishi T, Nakamura T, et al. Klotho protein protects against endothelial dysfunction. Biochem Biophys Res Commun 1998;248(2):324-9.
Nagai R, Saito Y, Ohyama Y, et al. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci 2000;57(5):738-46.
Nagai T, Yamada K, Kim HC, et al. Cognition impairment in the genetic model of aging klotho gene mutant mice: a role of oxidative stress. Faseb J 2003;17(1):50-2.
Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001;163(7):1693-722.
Pratico D, Basili S, Vieri M, et al. Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress. Am J Respir Crit Care Med 1998;158(6):1709-14.
Sato A, Hirai T, Imura A, et al. Morphological mechanism of the development of pulmonary emphysema in klotho mice. Proc Natl Acad Sci U S A 2007;104(7):2361-5.
Yamada Y, Ando F, Niino N, Shimokata H. Association of polymorphisms of the androgen receptor and klotho genes with bone mineral density in Japanese women. J Mol Med 2005;83(1):50- 7.
Dirksen A. Is CT a new research tool for COPD? Clin Respir J 2008;2 Suppl 1:76-83.
Nishino M, Washko GR, Hatabu H. Volumetric expiratory HRCT of the lung: clinical applications. Radiol Clin North Am;48(1):177- 83.
Nakano Y, Van Tho N, Yamada H, Osawa M, Nagao T. Radiological approach to asthma and COPD--the role of computed tomography. Allergol Int 2009;58(3):323-31.
Journals System - logo
Scroll to top