Manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with risk of early-onset prostate cancer

Prostate cancer continues to be the most frequently diagnosed neoplasm, and the second leading cause of cancer-related mortality in men. Oxidative stress may enhance prostatic carcinogenesis. Manganese superoxide dismutase (MnSOD) is the only known superoxide scavenger in mitochondria. It plays a key role in antioxidant defense as mitochondria are important for oxidative metabolism coupled to the electron transport chain and oxidative phosphorylation and hence, ROS production. A T-->C single nucleotide substitution, resulting in a Val-->Ala change at position 9 (Ala-9Val), which alters the secondary structure of the protein, has been noted to affect transport of MnSOD into the mitochondria. We have determined the MnSOD genotype in 85 prostate cancer cases and 151 control subjects. Ala-9Val polymorphism was determined using real time polymerase chain reaction (PCR) amplification with fluorescently labeled primers. No significant difference was found in prostate cancer susceptibility in the subjects with Ala/Ala and Val/Ala genotype compared with Val/Val genotype (Odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.69-2.42; p = 0.416). We did not observe an association of the MnSOD genotype or allele frequency between subgroups of cases divided by disease status (aggressive vs. non-aggressive prostate cancer). However, in the analyses stratified by the age at diagnosis we have observed that men homozygous for Ala had a 5.2-fold increased risk of early-onset prostate cancer (under age of 65) compared to men homozygous for Val allele (p = 0.05). These data suggest that Ala/Ala MnSOD genotype in the Macedonian population could have an influence on early onset of prostate cancer, but no impact on the subsequent development of the disease.     

Genetic polymorphism of manganese superoxide dismutase (MnSOD) and breast cancer susceptibility

Within mitochondria, manganese superoxide dismutase (MnSOD) provides a major defence against oxidative damage by reactive oxygen species (ROS). An alanine-9valine (Ala-9Val) polymorphism in the mitochondrial targeting sequence of MnSOD has been described and has recently been associated with risk of human breast cancer. Our present case-control study was performed to explore the association between MnSOD genetic polymorphism and individual susceptibility to breast cancer. Ala-9Val polymorphism in the signal sequence of the protein for MnSOD was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a study population. There was no significant difference in risk for breast cancer development between patients positive and negative for the MnSOD Ala allele with adjusted odds ratio (OR): 0.86 (95% confidence interval (CI(0.43 to 1.72). When MnSOD Ala was combined with either cytochrome P450 1B1 CYP1B1*1 and catechol O-methyltransferase COMT-L (V158M) genotypes, the risk for developing breast cancer was significantly increased in patients with a body mass index (BMI) greater than 24 kg m(-2) (OR: 1.42 (95%CI=1.04-1.93)).     

Link between MnSOD Ala16Val (rs4880) polymorphism and asthma risk is insignificant from sequential meta-analysis

The mitochondrial manganese superoxide dismutase (MnSOD) enzyme protects lungs against oxidative stress by neutralizing the free radical superoxide produced in the respiratory function. This has relevance to asthma. Therefore, it is of interest to describe the potential effect of MnSOD Ala16Val genetic polymorphism to asthma risk. Known data in this context is inconclusive in nature. The possible link between MnSOD Ala16Val polymorphism and asthma is explored using sequence meta-analysis. Data from the pooled analysis of MnSOD Ala16Val polymorphism using five genetic models i.e., allelic (Val vs. Ala: p=0.846; OR=1.033, 95% CI=0.742 to 1.440) is discussed. Homozygous (Val Val vs. Ala Ala: p=0.517; OR=1.307, 95% CI=0.582 to 2.932) and heterozygous (Val Ala vs. Ala Ala: p=0.307; OR=1.138, 95% CI=0.888 to 1.459) data using the described models are documented. Data from the dominant model (Val Val + Val Ala vs. Ala Ala: p=0.301; OR=1.289, 95% CI=0.797 to 2.085) and the recessive model (Val Val vs. Val Ala + Ala Ala: p=0.761; OR=0.924, 95% CI=0.555 to 1.538) analyses for several ethnic subgroups in this context is reported.     

DIO基因多态性与有氧耐力的相关性研究

目的:研究碘代甲状腺氨酸脱碘酶(DIO)基因多态性与有氧耐力的相关性,寻找与有氧耐力表型相关的分子标记。方法:应用基质辅助激光解吸电离飞行时间质谱检测技术,对123名中国北方汉族优秀长跑运动员(EEA)与127名中国北方汉族普通大学生(CG)DIO1基因C785T位点及DIO2基因的Thr92Ala和Gly3Asp位点进行解析并分析比较,其中优秀运动员又根据运动等级和运动项目分为国际健将与健将组(43vs80),及5/10km和马拉松组(92vs31)。结果:在DIO1的C785T位点及DIO2的Thr92Ala位点,各组间基因型和等位基因频率均无显著性差异(P>0.05);在DIO2的Gly3Asp位点,三种基因型在CG组与国际健将组、CG组与马拉松组间的分布均差异显著(P<0.05),其中TT基因型在CG组中不表达,仅存在于EEA组,但频率很低。DIO2的Thr92Ala及Gly3Asp位点处于强连锁不平衡,CT单体型在男CG组与女CG组、男CG组与男EEA组间分布均差异显著(P<0.05),在男CG组与男健将组、男马拉松组间的分布也均差异显著(P<0.05),TC单体型则在女CG组与女国际健将组、女5000m和10000m组间的分布差异显著(P<0.05)。结论:DIO2基因Thr92Ala及Gly3Asp位点的CT单体型分布具有性别差异,是男子EEA有氧耐力素质的分子标记,可用于男子长跑健将级运动员及马拉松运动员的分子选材,TC单体型则是女子长跑国际健将运动员和5000m、10000m运动员有氧耐力素质的分子标记。     

SOD2 gene polymorphism and muscle damage markers in elite athletes

Abstract

Exercise-induced oxidative stress is a state that primarily occurs in athletes involved in high-intensity sports when pro-oxidants overwhelm the antioxidant defense system to oxidize proteins, lipids, and nucleic acids. During exercise, oxidative stress is linked to muscle metabolism and muscle damage, because exercise increases free radical production. The T allele of the Ala16Val (rs4880 C/T) polymorphism in the mitochondrial superoxide dismutase 2 (SOD2) gene has been reported to reduce SOD2 efficiency against oxidative stress. In the present study we tested the hypothesis that the SOD2 TT genotype would be underrepresented in elite athletes involved in high-intensity sports and associated with increased values of muscle and liver damage biomarkers. The study involved 2664 Caucasian (2262 Russian and 402 Polish) athletes. SOD2 genotype and allele frequencies were compared to 917 controls. Muscle and liver damage markers [creatine kinase (CK), creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP)] were examined in serum from 1444 Russian athletes. The frequency of the SOD2 TT genotype (18.6%) was significantly lower in power/strength athletes (n = 524) compared to controls (25.0%, p = 0.0076) or athletes involved in low-intensity sports (n = 180; 33.9%, p < 0.0001). Furthermore, the SOD2 T allele was significantly associated with increased activity of CK (females: p = 0.0144) and creatinine level (females: p = 0.0276; males: p = 0.0135) in athletes. Our data show that the SOD2 TT genotype might be unfavorable for high-intensity athletic events.     

Peak anaerobic power in master athletes

The age-related decline in maximal physical performance of healthy subjects may be attributed both to the aging process per se and/or to a progressive reduction in physical activity. In two groups of master athletes, power (P) or endurance (E) trained (n = 115; aged 40-78 years), the degree and rate of the age-related deterioration of the maximal instantaneous muscle power (peak power, Wpeak), and the relative contribution of quantitative (muscle mass) and qualitative factors possibly underlying such deterioration were determined. Two groups of young athletes (n = 20; 17-26 years) and healthy untrained subjects (U, n = 37; 22-67 years) were also tested for comparison. The following two variables were assessed, firstly the lower limb muscle plus bone volume (LMV) by anthropometry, and secondly Wpeak, by means of a standardized vertical jump off both feet, performed on a force platform. The results obtained were that LMV of E and P, as well as of U, was about the same between age 20 and 45 years, whereas at older ages a progressive reduction was observed; the LMV values were higher in P than in E and U.(ABSTRACT TRUNCATED AT 250 WORDS)     

Twitch contractile properties of plantar flexor muscles in power and endurance trained athletes

This study compared twitch contractile properties of plantar flexor muscles among three groups of 12 subjects each: endurance and power trained athletes and untrained subjects. The posterior tibial nerve was stimulated by supramaximal square wave pulses of 1-ms duration. Power trained athletes had higher twitch maximal force, maximal rates of force development and relaxation and also maximal voluntary contraction (MVC) force. The trained subjects had a smaller twitch maximal force: MVC force ratio and shorter twitch contraction and half-relaxation times than the untrained subjects with no significant differences between the two groups. Thus, the short time for evoked twitches in the athletes compared to the untrained subjects would seem unrelated to the type of training. It is concluded that power training induces a more evident increase of muscle force-generating capacity and speed of contraction and relaxation than endurance training. Accepted: 24 April 1999     

Biochemical and Stability Properties of Recombinant Human MnSOD

The light absorption spectral properties of recornbinant human MnSOD. which contains an N-terminal additional methionyl residue, were investigated as a function of pH in the range 4.5–10.5. Whereas the extinction coefficient, ?_M at the UV maximum (282 nm) was essentially independent of pH, the ?_M values of the visible spectrum maximum (482 nm) displayed a bell-shaped dependence with a plateau between pH 6.5 and B. Those spectral changes were reversible and the enzymatic activity was not affected by exposure to buffered solutions at 25°C in the pH range 5–10.5. The stability of MnSOD was determined between 25 and 60°C at two different pH: 6.5 and 8.2. The enzyme was found to be considerably more stable at pH 6.5 than at pH 8.2, both toward aggregation and degradation. The gel permeation properties of MnSOD were investigated: the enzyme is a tetramer, with a subunit of 22.2 kD; however. it elutes from a Superose 12 column (Pharmacia) with an apparent molecular weight of ～60kD. Under dissociative conditions (such as guanidine-HCI). molecular weights corresponding to the dimer and monomer could also be demonstrated. It thus appears that the tetramer adopts a non-globular shape. which causes the deviation from the Stokes radius corresponding to its molecular weight.     

THE ASSOCIATION BETWEEN ACE GENE VARIATION AND AEROBIC CAPACITY IN WINTER ENDURANCE DISCIPLINES

The aim of the study was to examine the possible relationship between I/D polymorphism of ACE gene and selected indices of aerobic capacity among male and female athletes practising winter endurance sports. Sixty-six well-trained athletes (female n = 26, male n = 40), aged 18.4 ± 2.8 years, representing winter endurance sports (cross-country skiing, n = 48; biathlon, n = 8; Nordic combined, n = 10) participated in the study. Genotyping for ACE I/D polymorphism was performed using polymerase chain reaction. Maximal oxygen consumption (VO₂max), maximal running velocity (V_max) and running velocity at anaerobic threshold (V_AT4) were determined in an incremental test to volitional exhaustion on a motorized treadmill. The ACE genotype had no significant effect on absolute VO₂max, relative VO₂max (divided by body mass or fat free body mass), V_AT4 or V_max. No interaction effect of gender x ACE genotype was found for each of the examined aerobic capacity indices. ACE gene variation was not found to be a determinant of aerobic capacity in either female or male Polish, well-trained endurance athletes participating in winter sports.     

我国中华按蚊群体分子遗传多态研究

利用RAPD-PCR技术研究了采自我国9省10个代表点的中华按蚊Anopheles sinensis自然群体的遗传多态现象,根据23个RAPD等位基因位点进行了分析。结果显示：①多态位点比例为68.2%～86.4%,期望平均杂合度为0.249～0.348,说明中华按蚊群体具广泛的遗传多态现象;②利用3种方法计算Fst和θ,平均值为0.069～0.111,相应的迁移率Nm为2.0～3.4,表明基因流水平较低;③中华按蚊各自然群体间的遗传一致性达0.8795～0.9973,平均遗传距离为0.041±0.033,属种内变异范围。聚类分析显示,群体间遗传距离与地理位置无对应关系。     

Genetic polymorphism of human salivary proline-rich proteins: Further genetic analysis

Electrophoresis of concentrated parotid saliva on slab polyacrylamide gels negatively stained with 3,3-dimethoxybenzidine and hydrogen peroxide (DMB stain) showed nine phenotypes among the proline-rich proteins. These phenotypes are the expression of four autosomal codominant alleles. Gene frequencies are, for Caucasians, Pr ¹=0.640, Pr ¹=0.005, Pr ²=0.080, Pr ²=0.275; for Negroes, Pr ¹=0.700, Pr ¹=0.050, Pr ²=0.080, Pr ²=0.170; for Chinese, Pr ¹=0.770, Pr ¹=0, Pr ²=0, Pr ²=0.230. The presence or absence of another pair of proteins giving the same negative staining is inherited as an autosomal dominant trait (Db). Homozygous Db + + and heterozygous Db + – individuals could not be distinguished. The genetic determinant (Db) for this pair of proteins is either closely linked to or part of the Pr locus. Gene frequencies are, for Caucasians, Db ⁺=0.12, Db ^–=0.88; for Negroes, Db ⁺=0.56, Db ^–=0.44; for Chinese, Db ⁺=0.07, Db ^–=0.93.This study was supported by a grant from the National Institutes of Dental Research (9-R01-DE-03685-08) and in part by grant GM 15422 from the National Institutes of Health.     

Evolution of balanced genetic polymorphism

Extreme genetic polymorphism maintained by balancing selection (so called because many alleles are maintained in a balance by a mechanism of rare allele advantage) is intimately associated with the important task of self/non-self-discrimination. Widely disparate self-recognition systems of plants, animals and fungi share several general features, including the maintenance of large numbers of alleles at relatively even frequency, and persistence of this variation over very long time periods. Because the evolutionary dynamics of balanced polymorphism are very different from those of neutral genetic variation, data on balanced polymorphism have been used as a novel source for inference of the history of populations. This review highlights the unique evolutionary properties of balanced genetic polymorphism, and the use of theoretical understanding in analysis and application of empirical data for inference of population history. However, a second goal of this review is to point out where current theory is incomplete. Recent observations suggest that entirely novel selective forces may act in concert with balancing selection, and these novel forces may be extremely potent in shaping genetic variation at self-recognition loci.     

Increased p wave dispersion in elite athletes

Background

Few studies have been performed on P wave indices in athletes. The aim of this study was to determine the behaviour of maximum P wave duration (Pmax), minimum P wave duration (Pmin) and P wave dispersion (PWD) in young high performance athletes, as well as the relationship of PWD with training history, heart rate (HR) and echocardiographic parameters.

Methods

We performed a cross-sectional observational study in 38 athletes of high performance in sports: water polo, distance running and weight lifting compared with 34 sedentary controls.

Results

The average age in both groups was 20.6 years. Note that PWD was increased in athletes (57 ± 14 ms vs. 40 ± 12 ms, p <0.001) while Pmin was significantly lower (57 ± 13 ms vs. 72 ± 13 ms, p <0.001), and there was no difference when comparing Pmax (114 ± 9 ms vs. 117 ± 14 ms, p> 0.05). The correlation between the duration of training (r = 0.511) and resting HR (r = 0.461) with PWD was significant (p <0.01).

Conclusions

PWD is increased in young athletes of high performance and was positively correlated with duration of training and baseline HR. The increase in PWD was secondary to a significant decrease in Pmin.     

Effective utilization of genetic information for athletes and coaches: focus on ACTN3 R577X polymorphism

Training variants (type, intensity, and duration of exercise) can be selected according to individual aims and fitness assessment. Recently, various methods of resistance and endurance training have been used for muscle hypertrophy and VO₂max improvement. Although several genetic variants are associated with elite athletic performance and muscle phenotypes, genetic background has not been used as variant for physical training. ACTN3 R577X is a well-studied genetic polymorphism. It is the only genotype associated with elite athletic performance in multiple cohorts. This association is strongly supported by mechanistic data from an Actn3-knockout mouse model. In this review, possible guidelines are discussed for effective utilization of ACTN3 R577X polymorphism for physical training.     

The evolution, maintenance and adaptive function of genetic colour polymorphism in birds

The hypothesis that ornaments can honestly signal quality only if their expression is condition-dependent has dominated the study of the evolution and function of colour traits. Much less interest has been devoted to the adaptive function of colour traits for which the expression is not, or is to a low extent, sensitive to body condition and the environment in which individuals live. The aim of the present paper is to review the current theoretical and empirical knowledge of the evolution, maintenance and adaptive function of colour plumage traits for which the expression is mainly under genetic control. The finding that in many bird species the inheritance of colour morphs follows the laws of Mendel indicates that genetic colour polymorphism is frequent. Polymorphism may have evolved or be maintained because each colour morph facilitates the exploitation of alternative ecological niches as suggested by the observation that individuals are not randomly distributed among habitats with respect to coloration. Consistent with the hypothesis that different colour morphs are linked to alternative strategies is the finding that in a majority of species polymorphism is associated with reproductive parameters, and behavioural, life-history and physiological traits. Experimental studies showed that such covariations can have a genetic basis. These observations suggest that colour polymorphism has an adaptive function. Aviary and field experiments demonstrated that colour polymorphism is used as a criterion in mate-choice decisions and dominance interactions confirming the claim that conspecifics assess each other's colour morphs. The factors favouring the evolution and maintenance of genetic variation in coloration are reviewed, but empirical data are virtually lacking to assess their importance. Although current theory predicts that only condition-dependent traits can signal quality, the present review shows that genetically inherited morphs can reveal the same qualities. The study of genetic colour polymorphism will provide important and original insights on the adaptive function of conspicuous traits.     

Sheep blood polymorphism and genetic divergence between French Rambouillet and Spanish Merino: role of genetic drift

Rambouillet sheep originating from Spanish Merino have been maintained in France as a small and closed flock since their importation. After 190 years of independent evolution, the flock has markedly differentiated from its Spanish parental population. The observed differences between them were characterized by the fixation in Rambouillet of the Mb and F30 alleles, which occurred in Spanish Merino with frequencies of 0.90 and 0.80 respectively (at two distinct blood group loci M and F30) and by the absence in Rambouillet of other alleles or phenogroups (at the Tf and the A, B, C blood group loci) which were observed in Spanish Merino with frequencies ranging from 0.10 to 0.28. On the basis of their phenotypic distributions at 11 blood polymorphic loci, the two populations differed significantly from each other (total chi 2 values = 352.62, 23 df, P less than 0.001). By comparing the observed magnitude of gene frequency differences between Rambouillet and Spanish Merino with the estimate of inbreeding coefficient for Rambouillet obtained from pedigrees, it appeared that the observed genetic differences could be attributed to the evolutionary change due to random drift in the small and closed flock of Rambouillet.     

Modeling and phylogeny analysis of bread wheat MnSOD

Superoxide dismutase (SOD) acts as first line of defense against oxidative and genetic stress. Manganese superoxide dismutase (MnSOD), found in mitochondria or peroxisomes, contains Mn(III) at the active site. Therefore, it is of interest to study MnSOD from bread wheat (a grain crop). However, a structure model is not yet solved for bread wheat MnSOD. Hence, we describe the structure model of bread wheat MnSOD developed using homology model. The model provides molecular insight to metal binding molecular function towards the understanding of oxidative stress resistance in plants. The distinction of bread wheat (a monocot) MnSOD from dicots is also shown using phylogenetic analysis.