Many potentially significant genetic variants related to oxidative stress have been identified and performance in endurance sports is a multi-factorial phenotype. Thus, it was decided to investigate the influences of the haptoglobin (Hp), MnSOD (Val9Ala), CAT (21A/T), GPX1 (Pro198Leu), ACE, glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes' polymorphisms on the oxidative stress and damage suffered by human athletes (runners). Blood samples taken immediately after a race were submitted to genotyping, comet and TBARS assays, biochemical analyses of creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). MnSOD significantly influenced results of CK and a possible association between Hp1F-1S and Hp1S-2 genotypes with a superior TBARS values was found. Higher or lower TBARS and CK values or DNA damage also depended on the interaction between Hp and ACE or GST genotypes, indicating that MnSOD and Hp polymorphisms can be determining factors in performance, at least for runners.

ABSTRACT. Chronic myeloid leukemia is a hematopoietic stem cell disorder that causes uncontrolled proliferation of white blood cells. Although the clinical and biological aspects are well documented, little is known about individual susceptibility to this disease. We conducted a case-control study analyzing the prevalence of the polymorphisms MTHFR C677T, MTHFR A1298C, del{GSTM1}, del{GSTT1}, and haptoglobin in 105 patients with chronic myeloid leukemia (CML) and 273 healthy controls, using PCR-based methods. A significant association with risk of developing CML was found for MTHFR 1298AA (odds ratio (OR) = 1.794; 95% confidence interval (CI) = 1.14-2.83) and GSTM1 non-null (OR = 1.649; 95%CI = 1.05-2.6) genotypes, while MTHFR 1298AC (OR = 0.630; 95%CI = 0.40-G.S. Lordelo et al. 1014©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (2): 1013-1026 (2012) 0.99) and GSTM1 null (OR = 0.606; 95%CI = 0.21-0.77) genotypes significantly decreased this risk. There appeared to be selection for heterozygosity at the MTHFR 1298 locus. The considerable range of variation in this and other human populations may be a consequence of distinctive processes of natural selection and adaptation to variable environmental conditions. The Brazilian population is very mixed and heterogeneous; we found these two loci to be associated with CML in this population.

No abstract

BackgroundNormal cellular metabolism is well established as the source of endogenous reactive oxygen species which account for the background levels of oxidative DNA damage detected in normal tissue. Hydrogen peroxide imposes an oxidative stress condition on cells that can result in DNA damage, leading to mutagenesis and cell death. Several potentially significant genetic variants related to oxidative stress have already been identified, and angiotensin I-converting enzyme (ACE) inhibitors have been reported as possible antioxidant agents that can reduce vascular oxidative stress in cardiovascular events.MethodsWe investigate the influences of haptoglobin, manganese superoxide dismutase (MnSOD Val9Ala), catalase (CAT -21A/T), glutathione peroxidase 1 (GPx-1 Pro198Leu), ACE (I/D) and gluthatione S-transferases GSTM1 and GSTT1 gene polymorphisms against DNA damage and oxidative stress. These were induced by exposing leukocytes from peripheral blood of healthy humans (N = 135) to hydrogen peroxide (H2O2), and the effects were tested by comet assay. Blood samples were submitted to genotyping and comet assay (before and after treatment with H2O2 at 250 μM and 1 mM).ResultsAfter treatment with H2O2 at 250 μM, the GPx-1 polymorphism significantly influenced results of comet assay and a possible association of the Pro/Leu genotype with higher DNA damage was found. The highest or lowest DNA damage also depended on interaction between GPX-1/ACE and Hp/GSTM1T1 polymorphisms when hydrogen peroxide treatment increased oxidative stress.ConclusionsThe GPx-1 polymorphism and the interactions between GPX-1/ACE and Hp/GSTM1T1 can be determining factors for DNA oxidation provoked by hydrogen peroxide, and thus for higher susceptibility to or protection against oxidative stress suffered by healthy individuals.

Context: Exhausting exercise, increasing reactive oxygen species, can overwhelm the endogenous antioxidant system's capacity, resulting in oxidative damage to DNA. Deficient antioxidant defenses, influenced by certain genetic polymorphisms, may contribute. Aims: We aimed to investigate whether carotenoid-rich oil from pequi (Caryocar brasiliense) could decrease DNA damage in athletes submitted to increased hydrogen peroxide (H 2 O 2 ) conditions and in those less genetically favored by antioxidant defenses. Methods and Material: Runners' blood (N = 125) was analyzed after races under the same environment, type, intensity and length of weekly training conditions, before and after 14 days of pequi-oil supplementation. DNA damage was assessed by comet assay before and after H 2 O 2 exposure, with gene polymorphisms of MnSOD Val9Ala, CAT -21A/T, GPx-1 Pro198Leu, del{GSTM1}, del{GSTT1}, ACE and Haptoglobin. Results: Without additional oxidative stress imposed by H 2 O 2 , pequi oil was particularly efficient reducing DNA damage for women, age group of 20-40 years, distance of 8-10 Km and genotypes MnSOD Val/Ala, CAT TT, GPx-1 Pro/Leu, GSTM1 null, GSTT1 non-null, ACE DD and II and Hp1F-2. For treatment with H 2 O 2 at 0.25 mM, pequi oil resulted in decreased DNA damage only for running 16-21 Km; for treatment with 1 mM, decrease was for 20-40 years and genotypes GPx-1 Pro/Pro and ACE ID. Conclusions: Pequi oil's effect on exercise-induced DNA damage was therefore influenced by sex, age and genetic polymorphisms, indicating that: long-distance races can be harmful, mainly for older athletes, due to oxidative stress above organism adaptability; genotypes showed different responses; under increased H 2 O 2 conditions, GPx-1 Pro/Pro and ACE ID genotypes were more responsive to antioxidant supplementation. IntroductIonHydrogen peroxide (H 2 O 2 ) is an important representative reactive oxygen species (ROS) that arises during the aerobic respiration process and from other cellular sources.[ [2] However, oxidative stress can be caused by excessive production Key-words: reactive oxygen species; hydrogen peroxide; exercise-induced oxidative stress; exercise-induced DNA damage; comet assay; gene polymorphisms related to oxidative stress Key Messages: the present study can help broaden knowledge of how antioxidant supplementation affects exercise-induced DNA damage and how individual athletic genetic makeup can affect the way athletes respond to antioxidant supplementation against exercise-induced DNA damage.Correspondence Phone numbers: +55 61 3107-3085, Fax: +55 61 3273-4942

Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. The results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.

Physical training induces beneficial adaptations, but exhausting exercise increases reactive oxygen species, which can cause muscular injuries with consequent inflammatory processes, implying jeopardized performance and possibly overtraining. Acute strenuous exercise almost certainly exceeds the benefits of physical activity; it can compromise performance and may contribute to increased future risk of cardiovascular disease (CVD) in athletes. Polymorphisms in the muscle-type creatine kinase (CK-MM) gene may influence performance and adaptation to training, while many potentially significant genetic variants are reported as risk factors for CVD. Therefore, we investigated the influence of polymorphisms in CK-MM TaqI and NcoI, methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and C-reactive protein (CRP G1059C) genes on exercise-induced damage and inflammation markers. Blood samples were taken immediately after a race (of at least 4 km) that took place outdoors on flat tracks, and were submitted to genotyping and biochemical evaluation of aspartate aminotransferase (AST), CK, CRP and high-sensitivity CRP (hs-CRP). CK-MM TaqI polymorphism significantly influenced results of AST, CK and hs-CRP, and an association between MTHFR C677T and A1298C with CRP level was found, although these levels did not exceed reference values. Results indicate that these polymorphisms can indirectly influence performance, contribute to higher susceptibility to exercise-induced inflammation or protection against it, and perhaps affect future risks of CVD in athletes.

ABSTRACT. Essential hypertension is a complex and multifactorial trait; genetic and environmental factors interact to produce the final phenotype. Studies have demonstrated association of hypertension with varied gene polymorphisms. However, demonstration of common genetic causes in the general population remains elusive. We investigated a possible association between hypertension and haptoglobin, angiotensin I-converting enzyme (ACE), glutathione S-transferases GSTM1 and GSTT1, MnSOD (Val9Ala), CAT (-21A/ T), and GPX1 (Pro198Leu) gene polymorphisms in an urban Brazilian population group from Brasília. Although ACE has been reported to be one of the main polymorphisms associated with hypertension, we found no association with ACE's specific genotypes. However, a possible 2167 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 9 (4): 2166-2175 (2010) Gene polymorphisms linked to hypertension in Brazil association with Hp1-1 and MnSOD Val/Ala genotypes suggests that, at least for the Brazilian population, polymorphisms related to oxidative stress should be more deeply investigated.