Variant Polymorphisms of GST and XRCC Genes and the Early Risk of Age Associated Disease in Kazakhstan
It is believed that DNA damaging toxic metabolites contributes to the development of different pathological conditions. To prevent harmful influence of toxic agents, cells developed number of protecting mechanisms, such as enzymatic reaction of detoxification of reactive metabolites and repair of DNA damage. The aim of the study was to examine the association between polymorphism of GSTT1/GSTM1 and XRCC1/3 genes and coronary artery disease (CAD) incidence. To examine a polymorphism of these genes in CAD susceptibility in patients and controls, PCR based genotyping assay was performed. For GST genes, frequency of GSTM1 null genotype among CAD affected group was significantly increased than in control group (P<0.001). Frequencies of the GSTT1 null and positive alleles are almost equal in both groups (P>0.1). We found that neither XRCC1 Arg399Gln nor XRCC3 Thr241Met were associated with CAD risk. Obtained data suggests that GSTM1 null genotype carriers are more susceptible to CAD development.
[1] Abbate A, Bussani R, Amin MS, Vetrovec GW, Baldi A. 2006 Acute myocardial infarction and heart failure: Role of apoptosis. Int J Biochem Cell Biol; 38:1834-1840.
[2] World Health Organization. World Health Statistics Annual 2005 (online) Geneva: World Health Organization; 2005. Accessed on 10
August, 2007 URL: http://www.who.int/en/
[3] Heart Disease and Stroke Statistics ÔÇö 2005 Update, American Heart Association.
[4] Ministry of Public Health of the Republic of Kazakhstan. The report about the number of diseases, registered for the first time with
determined diagnosis (online). URL:
http://www.mz.gov.kz/index.php?wakka=/ Eng/ Medical Statistics
[5] Ministry of Public Health of the Republic of Kazakhstan. Report about
the socially significant diseases, registered for the first time with
determinate diagnosis in the first half-year of 2005-2006 years (online).URL: http://www.mz.gov.kz/index.php?wakka= /Eng/ Medical Statistics
[6] Sprengers RW, Janssen K J., Moll FL, Verhaar MC, van der Graaf Y,
SMART Study Group. 2009 Prediction rule for cardiovascular events
and mortality in peripheral arterial disease patients: Data from the
prospective Second Manifestations of ARTerial disease (SMART)
cohort study. J Vasc Surg. 50, 1369-1376.
[7] Cacoub PP, Abola MT, Baumgartner I, Bhatt DL, Creager MA, Liau
CS, Goto S, Röther J, Steg PG, Hirsch AT, on behalf of the REACH
Registry Investigators, 2009. Cardiovascular risk factor control and
outcomes in peripheral artery disease patients in the Reduction of
Atherothrombosis for Continued Health (REACH) Registry
Atherosclerosis; 204: 86-92.
[8] Niccoli G, Iacoviello L, Cianflone D, Crea F. Coronary risk factors: new
perspectives. International Journal of Epidemiology. 2001; 30: S41-S47.
[9] Csiszar A, Podlutsky A, Wolin MS, Losonczy G, Pacher P, Ungvari Z.
Oxidative stress and accelerated vascular aging: implications for
cigarette smoking. Front Biosci. 2009; 14: 3128-3144.
[10] De Bont R, van Larebeke N. Endogenous DNA damage in humans: a
review of quantitative data. Mutagenesis. 2004; 19: 169-185.
[11] Olinski R, Siomek A, Rozalski R, Gackowski D, Foksinski M, Guz J,
Dziaman T, Szpila A, Tudek B. Oxidative damage to DNA and
antioxidant status in aging and age-related diseases. Acta Biochim Pol.
2007;54(1):11-26.
[12] Mahmoudi M, Mercer J, Bennett M. DNA damage and repair in atherosclerosis. Cardiovascular Research. 2006; 71: 259 - 268.
[13] van Schooten FJ, Hirvonen A, Maas LM, de Mol BA, Kleinjans JCS,
Bell DA, Durrer JD. Putative susceptibility markers of coronary artery
disease: association between VDR genotype, smoking, and aromatic
DNA adduct levels in human right atrial tissue. FASEB J. 1998; 12:
1409–1417.
[14] Izzotti A, Cartiglia C, Lewtas J. Increased DNA alterations in
atherosclerotic lesions of individuals lacking the GSTM1 genotype. The
FASEB Journal. 2001; 15: 752-757.
[15] Tekeli A, Isbir S, Ergen A, Görmüş U, Bozkurt N, Timirci O, Arsan S,
Isbir T. APE1 and XRCC3 polymorphisms and myocardial infarction. In
Vivo. 2008; 22(4):477-9.
[16] Kiyohara C, Takayama K, Nakanishi Y. 2006 Association of genetic
polymorphisms in the base excision repair pathway with lung cancer
risk: a meta-analysis. Lung Cancer; 54: 267-83.
[17] Mohrenweiser HW, Wilson III DM, Jones IJ. 2003 Challenges and
complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA
repair genes. Mutation Research; 526: 93–125.
[18] Shen H, Wang X, Hu Z, Zhang Z, Xu Y, Hu Y, Guo J, Wei Q.
Polymorphisms of DNA repair gene XRCC3 Thr241Met and risk of
gastric cancer in a Chinese population. Cancer Letters. 2004; 206: 51–
58.
[19] Popanda O, Schattenberg T, Phong CT, Butkiewicz D, Risch A, Edler L,
Kayser K, Dienemann H, Schulz V, Drings P, Bartsch H, Schmezer P.
2004 Specific combinations of DNA repair gene variants and increased
risk for non-small cell lung cancer. Carcinogenesis; 25:2433-2441.
[20] Misra RR, Ratnasinghe D, Tangrea JA, Virtamo J, Andersen MR,
Barrett M, Taylor PR, Albanes D. 2003 Polymorphisms in the DNA
repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung
cancer among male smokers in Finland. Cancer Lett; 191:171-178.
Hayes JD, Flanagan JU, Jowsey IR. 2005 Glutathione transferases.
Annu Rev Pharmacol Toxicol; 45: 51-88.
[21] Bolegenova NK, Bekmanov BO, Djansugurova LB, Bersimbaev RI,
Salama SA, Au WW. 2009 Genetic polymorphisms and expression of
minisatellite mutations in a 3-generation population around the
Semipalatinsk nuclear explosion test-site, Kazakhstan. Int J Hyg Environ
Health. 212: 654-60.
[22] Wilson MH, Grant PJ, Kain K, Warner DP, Wild CP. 2003 Association
between the risk of coronary artery disease in South Asians and a
deletion polymorphism in glutathione S-transferase M1. Biomarkers; 8:
43-50.
[23] Wilson MH, Grant PJ, Hardi LJ. 2000 Glutathione S-transferase M1 null
genotype is associated with a decreased risk of myocardial infarction.
The FASEB Journal; 14: 791-796.
[24] Girisha KM, Gilmour A, Mastana S, Singh VP, Sinha N, Tewari S,
Ramesh V, Sankar VH, Agrawal S. 2004 T1 and M1 polymorphism in
glutathione S-transferase gene and coronary artery disease in North
Indian population. Ind J Med. Sci.; 58. 520-526.
[25] Au WW, Salama SA. 2005 Use of Biomarkers to Elucidate Genetic
Susceptibility to Cancer. Environ Molecular Mutagenesis; 45: 222-228.
[26] Abu-Amero KK, Al-Boudari OM, Mohamed GH, Dzimiri N 2006. T
null and M null genotypes of the glutathione S-transferase gene are risk
factor for CAD independent of smoking. BMC Medical Genetics; 38: 7-
38.
[27] Salama SA, Au WW, Hunter GC, Sheahan RG, Badary OA, Abdel-
Naim AB, Hamada FM. 2002 Polymorphic metabolizing genes and
susceptibility to atherosclerosis among cigarette smokers. Environ Mol
Mutagen; 40:153-60.
[28] Guven M, Guven GS, Oz E, Ozaydin A, Batar B, Ulutin T,
Hacihanefioglu S, Domanic N. 2007 DNA repair gene XRCC1 and XPD
polymorphisms and their association with coronary artery disease risks
and micronucleus frequency. Heart Vessels; 22:355-60.
[29] Tuimala J, Szekely G, Wikman H, Jarventaus H, Hirvonen A, Gundy S,
Norppa H. 2004 Genetic polymorphisms of DNA repair and xenobioticmetabolizing
enzymes: effects on levels of sister chromatid exchanges
and chromosomal aberrations. Mutation Res; 554: 319–333.
[1] Abbate A, Bussani R, Amin MS, Vetrovec GW, Baldi A. 2006 Acute myocardial infarction and heart failure: Role of apoptosis. Int J Biochem Cell Biol; 38:1834-1840.
[2] World Health Organization. World Health Statistics Annual 2005 (online) Geneva: World Health Organization; 2005. Accessed on 10
August, 2007 URL: http://www.who.int/en/
[3] Heart Disease and Stroke Statistics ÔÇö 2005 Update, American Heart Association.
[4] Ministry of Public Health of the Republic of Kazakhstan. The report about the number of diseases, registered for the first time with
determined diagnosis (online). URL:
http://www.mz.gov.kz/index.php?wakka=/ Eng/ Medical Statistics
[5] Ministry of Public Health of the Republic of Kazakhstan. Report about
the socially significant diseases, registered for the first time with
determinate diagnosis in the first half-year of 2005-2006 years (online).URL: http://www.mz.gov.kz/index.php?wakka= /Eng/ Medical Statistics
[6] Sprengers RW, Janssen K J., Moll FL, Verhaar MC, van der Graaf Y,
SMART Study Group. 2009 Prediction rule for cardiovascular events
and mortality in peripheral arterial disease patients: Data from the
prospective Second Manifestations of ARTerial disease (SMART)
cohort study. J Vasc Surg. 50, 1369-1376.
[7] Cacoub PP, Abola MT, Baumgartner I, Bhatt DL, Creager MA, Liau
CS, Goto S, Röther J, Steg PG, Hirsch AT, on behalf of the REACH
Registry Investigators, 2009. Cardiovascular risk factor control and
outcomes in peripheral artery disease patients in the Reduction of
Atherothrombosis for Continued Health (REACH) Registry
Atherosclerosis; 204: 86-92.
[8] Niccoli G, Iacoviello L, Cianflone D, Crea F. Coronary risk factors: new
perspectives. International Journal of Epidemiology. 2001; 30: S41-S47.
[9] Csiszar A, Podlutsky A, Wolin MS, Losonczy G, Pacher P, Ungvari Z.
Oxidative stress and accelerated vascular aging: implications for
cigarette smoking. Front Biosci. 2009; 14: 3128-3144.
[10] De Bont R, van Larebeke N. Endogenous DNA damage in humans: a
review of quantitative data. Mutagenesis. 2004; 19: 169-185.
[11] Olinski R, Siomek A, Rozalski R, Gackowski D, Foksinski M, Guz J,
Dziaman T, Szpila A, Tudek B. Oxidative damage to DNA and
antioxidant status in aging and age-related diseases. Acta Biochim Pol.
2007;54(1):11-26.
[12] Mahmoudi M, Mercer J, Bennett M. DNA damage and repair in atherosclerosis. Cardiovascular Research. 2006; 71: 259 - 268.
[13] van Schooten FJ, Hirvonen A, Maas LM, de Mol BA, Kleinjans JCS,
Bell DA, Durrer JD. Putative susceptibility markers of coronary artery
disease: association between VDR genotype, smoking, and aromatic
DNA adduct levels in human right atrial tissue. FASEB J. 1998; 12:
1409–1417.
[14] Izzotti A, Cartiglia C, Lewtas J. Increased DNA alterations in
atherosclerotic lesions of individuals lacking the GSTM1 genotype. The
FASEB Journal. 2001; 15: 752-757.
[15] Tekeli A, Isbir S, Ergen A, Görmüş U, Bozkurt N, Timirci O, Arsan S,
Isbir T. APE1 and XRCC3 polymorphisms and myocardial infarction. In
Vivo. 2008; 22(4):477-9.
[16] Kiyohara C, Takayama K, Nakanishi Y. 2006 Association of genetic
polymorphisms in the base excision repair pathway with lung cancer
risk: a meta-analysis. Lung Cancer; 54: 267-83.
[17] Mohrenweiser HW, Wilson III DM, Jones IJ. 2003 Challenges and
complexities in estimating both the functional impact and the disease risk associated with the extensive genetic variation in human DNA
repair genes. Mutation Research; 526: 93–125.
[18] Shen H, Wang X, Hu Z, Zhang Z, Xu Y, Hu Y, Guo J, Wei Q.
Polymorphisms of DNA repair gene XRCC3 Thr241Met and risk of
gastric cancer in a Chinese population. Cancer Letters. 2004; 206: 51–
58.
[19] Popanda O, Schattenberg T, Phong CT, Butkiewicz D, Risch A, Edler L,
Kayser K, Dienemann H, Schulz V, Drings P, Bartsch H, Schmezer P.
2004 Specific combinations of DNA repair gene variants and increased
risk for non-small cell lung cancer. Carcinogenesis; 25:2433-2441.
[20] Misra RR, Ratnasinghe D, Tangrea JA, Virtamo J, Andersen MR,
Barrett M, Taylor PR, Albanes D. 2003 Polymorphisms in the DNA
repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung
cancer among male smokers in Finland. Cancer Lett; 191:171-178.
Hayes JD, Flanagan JU, Jowsey IR. 2005 Glutathione transferases.
Annu Rev Pharmacol Toxicol; 45: 51-88.
[21] Bolegenova NK, Bekmanov BO, Djansugurova LB, Bersimbaev RI,
Salama SA, Au WW. 2009 Genetic polymorphisms and expression of
minisatellite mutations in a 3-generation population around the
Semipalatinsk nuclear explosion test-site, Kazakhstan. Int J Hyg Environ
Health. 212: 654-60.
[22] Wilson MH, Grant PJ, Kain K, Warner DP, Wild CP. 2003 Association
between the risk of coronary artery disease in South Asians and a
deletion polymorphism in glutathione S-transferase M1. Biomarkers; 8:
43-50.
[23] Wilson MH, Grant PJ, Hardi LJ. 2000 Glutathione S-transferase M1 null
genotype is associated with a decreased risk of myocardial infarction.
The FASEB Journal; 14: 791-796.
[24] Girisha KM, Gilmour A, Mastana S, Singh VP, Sinha N, Tewari S,
Ramesh V, Sankar VH, Agrawal S. 2004 T1 and M1 polymorphism in
glutathione S-transferase gene and coronary artery disease in North
Indian population. Ind J Med. Sci.; 58. 520-526.
[25] Au WW, Salama SA. 2005 Use of Biomarkers to Elucidate Genetic
Susceptibility to Cancer. Environ Molecular Mutagenesis; 45: 222-228.
[26] Abu-Amero KK, Al-Boudari OM, Mohamed GH, Dzimiri N 2006. T
null and M null genotypes of the glutathione S-transferase gene are risk
factor for CAD independent of smoking. BMC Medical Genetics; 38: 7-
38.
[27] Salama SA, Au WW, Hunter GC, Sheahan RG, Badary OA, Abdel-
Naim AB, Hamada FM. 2002 Polymorphic metabolizing genes and
susceptibility to atherosclerosis among cigarette smokers. Environ Mol
Mutagen; 40:153-60.
[28] Guven M, Guven GS, Oz E, Ozaydin A, Batar B, Ulutin T,
Hacihanefioglu S, Domanic N. 2007 DNA repair gene XRCC1 and XPD
polymorphisms and their association with coronary artery disease risks
and micronucleus frequency. Heart Vessels; 22:355-60.
[29] Tuimala J, Szekely G, Wikman H, Jarventaus H, Hirvonen A, Gundy S,
Norppa H. 2004 Genetic polymorphisms of DNA repair and xenobioticmetabolizing
enzymes: effects on levels of sister chromatid exchanges
and chromosomal aberrations. Mutation Res; 554: 319–333.
@article{"International Journal of Medical, Medicine and Health Sciences:51888", author = "Zeinep A. Berkimbayeva and Almagul T. Mansharipova and Elmira M. Khussainova and Leyla B. Djansugurova", title = "Variant Polymorphisms of GST and XRCC Genes and the Early Risk of Age Associated Disease in Kazakhstan", abstract = "It is believed that DNA damaging toxic metabolites contributes to the development of different pathological conditions. To prevent harmful influence of toxic agents, cells developed number of protecting mechanisms, such as enzymatic reaction of detoxification of reactive metabolites and repair of DNA damage. The aim of the study was to examine the association between polymorphism of GSTT1/GSTM1 and XRCC1/3 genes and coronary artery disease (CAD) incidence. To examine a polymorphism of these genes in CAD susceptibility in patients and controls, PCR based genotyping assay was performed. For GST genes, frequency of GSTM1 null genotype among CAD affected group was significantly increased than in control group (P0.1). We found that neither XRCC1 Arg399Gln nor XRCC3 Thr241Met were associated with CAD risk. Obtained data suggests that GSTM1 null genotype carriers are more susceptible to CAD development.
", keywords = "Cardiovascular disease, DNA reparation, gene polymorphism, risk factors, xenobiotic detoxification.", volume = "6", number = "11", pages = "547-6", }
