Are genes encoding proteoglycans really associated with the risk of anterior cruciate ligament rupture?

Proteoglycans are considered integral structural components of tendon and ligament and have been implicated in the resistance of compressive forces, collagen fibrillogenesis, matrix remodelling and cell signalling. Several sequence variants within genes encoding proteoglycans were recently implicated in modulating anterior cruciate ligament ruptures (ACLR). This study aimed to test the previously implicated variants in proteoglycan and vascular epithelial growth factor encoding genes with risk of ACLR in a population from Poland. A case control genetic association study was conducted using DNA samples from 143 healthy participants without a history of ACL injuries (99 male and 44 females) (CON group) and 229 surgically diagnosed ACLR participants (158 males and 71 females). All samples were genotyped for the ACAN: rs1516797, BGN: rs1042103, rs1126499, DCN: rs516115 and VEGFA: rs699947 variants. Main findings included the (i) ACAN rs1516797 G/T genotype which was underrepresented in the CON group (CON: 36%, n=52, ACLR: 49%, n=112, p=0.017, OR=1.68, 95% CI 1.09 to 2.57) when all participants were investigated and (ii) the BGN rs1042103 A allele was significantly under-represented in the male CON group compared to the male ACLR group (CON: 39%, n=78, ACLR: 49%, n=156, p=0.029, OR=1.5, 95% CI 1.05 to 2.15). Furthermore, BGN inferred haplotypes were highlighted with altered ACLR susceptibility. Although the study implicated the ACAN and BGN genes (combination of genotype, allele and haplotype) in modulating ACLR susceptibility, several differences were noted with previous published findings.

Overrepresentation of the COL3A1 AA genotype in Polish skiers with anterior cruciate ligament injury.

Although various intrinsic and extrinsic risk factors for anterior cruciate ligament (ACL) rupture have been identified, the exact aetiology of the injury is not yet fully understood. Type III collagen is an important factor in the repair of connective tissue, and certain gene polymorphisms may impair the tensile strength. The aim of this study was to examine the association of the COL3A1 rs1800255 polymorphism with ACL rupture in Polish male recreational skiers. A total of 321 male Polish recreational skiers were recruited for this study; 138 had surgically diagnosed primary ACL ruptures (ACL-injured group) and 183 were apparently healthy male skiers (control group - CON) who had no self-reported history of ligament or tendon injury. Both groups had a comparable level of exposure to ACL injury. Genomic DNA was extracted from the oral epithelial cells. All samples were genotyped on a real-time polymerase chain reaction instrument. The genotype distribution in the ACL-injured group was significantly different than in CON (respectively: AA=10.1 vs 2.2%, AG=22.5 vs 36.1, GG=67.4 vs 61.8%; p=0.0087). The AA vs AG+GG genotype of COL3A1 (odds ratio (OR)=5.05; 95% confidence interval (CI), 1.62-15.71, p=0.003) was significantly overrepresented in the ACL-injured group compared with CON. The frequency of the A allele was higher in the ACL-injured group (21.4%) compared with CON (20.2%), but the difference was not statistically significant (p=0.72). This study revealed an association between the COL3A1 rs1800255 polymorphism and ACL ruptures in Polish skiers.

Does the A9285G Polymorphism in Collagen Type XII α1 Gene Associate with the Risk of Anterior Cruciate Ligament Ruptures?

One of the most severe injuries sustained by athletes is rupture of the anterior cruciate ligament (ACL). Recent investigations suggest that a predisposition for ACL rupture may be the result of specific genetic sequence variants. In light of this, we decided to investigate whether the COL12A1 A9285G polymorphism was associated with ACL ruptures in Polish football players. We compared genotypic and allelic frequencies of the COL12A1 A9285G polymorphism in two groups of athletes: 91 male football players (23 ± 3 years) with surgically diagnosed primary ACL ruptures who qualified for ligament reconstruction (cases) and 143 apparently healthy, male football players of the same ethnicity, a similar age category, and a comparable level of exposure to ACL injury, who were without any self-reported history of ligament or tendon injury (controls). DNA samples extracted from the oral epithelial cells were genotyped by using a real-time polymerase chain reaction (Ri-Ti-PCR) method. The genotype distribution in the cases were not different from those in controls (p = 0.70). The frequency of the G allele was lower in the cases (18.1%) but not statistically significant (p = 0.40) when compared with controls (21.3%). Our results are in contradiction to the hypothesis that the COL12A1 A9285G polymorphism is associated with a predisposition for ACL injury. However, these conclusions should be supported with more experimental studies on COL12A1 polymorphisms.

THE GSTP1 c.313A>G POLYMORPHISM MODULATES THE CARDIORESPIRATORY RESPONSE TO AEROBIC TRAINING.

The GSTP1 c.313A>G polymorphism is a candidate to explain some of the individual differences in cardiorespiratory fitness phenotypes' responses to aerobic exercise training. We aim to explore the association between the GSTP1 c.313A>G polymorphism and the response to low-high impact aerobic exercise training. Sixty-six Polish Caucasian women were genotyped for the GSTP1 c.313A>G polymorphism; 62 of them completed 12-week aerobic (50-75% HRmax) exercise training and were measured for selected somatic features (body mass and BMI) and cardiorespiratory fitness indices - maximal oxygen uptake (VO2max, maximum heart rate (HRmax), maximum ventilation (VEmax) and anaerobic threshold (AT) - before and after the training period. Two-factor analysis of variance revealed a main training effect for body mass reduction (p=0.007) and BMI reduction (p=0.013), improvements of absolute and relative VO2max (both p<0.001), and increased VEmax (p=0.005), but not for changes in fat-free mass (FFM) (p=0.162). However, a significant training x GSTP1 c.313A>G interaction was found only for FFM (p=0.042), absolute and relative VO2max (p=0.029 and p=0.026), and VEmax (p=0.005). As the result of training, significantly greater improvements in VO2max, VEmax and FFM were gained by the GG+GA group compared to the AA genotype group. The results support the hypothesis that heterogeneity in individual response to training stimuli is at least in part determined by genetics, and GSTP1 c.313A>G may be considered as one (of what appear to be many) target polymorphisms to influence these changes.

Association of the 174 G/C polymorphism of the IL6 gene in Polish power-orientated athletes.

AIM: Interleukin-6 (IL6), has been called by some authors "an exercise factor" due to its pleiotropic effects during physical training. Several studies indicated that change in the guanine bases to cytosine at position -174 affects the transcription of the IL6 gene, and finally IL6 production level. The aim of this study was to perform confirmation studies to analyze the possible importance of the IL6 -174 G/C (rs1800795) polymorphism gene in Polish power-orientated athletes. METHODS: The study was carried out on two groups of men of the same Caucasian descent: 158 power-orientated athletes and 254 volunteers not involved in competitive sport. DNA was extracted from buccal cells donated by the subjects. Genotyping was carried out by polymerase chain reaction (PCR). Significance was assessed by Chi square (χ2) analysis. RESULTS: The results revealed that the frequency of the IL6 -174 GG genotype (53.16% vs. 35.82%; P=0.002) and G allele (68.67% vs. 57.87%; P=0.03) were significantly higher in the Polish power-orientated athletes compared to controls. CONCLUSION: These data suggest that the G allele could be one of the factors influencing the power-orientated sport performance. However, these conclusions should be supported with more experimental studies on other IL6 polymorphisms and other genes.

The +1245g/t polymorphisms in the collagen type I alpha 1 (col1a1) gene in polish skiers with anterior cruciate ligament injury.

OBJECTIVES: The aim of this study was to examine the association of +1245G/T polymorphisms in the COL1A1 gene with ACL ruptures in Polish male recreational skiers in a case-control study. METHODS: A total of 138 male recreational skiers with surgically diagnosed primary ACL ruptures, all of whom qualified for ligament reconstruction, were recruited for this study. The control group comprised 183 apparently healthy male skiers with a comparable level of exposure to ACL injury, none of whom had any self-reported history of ligament or tendon injury. DNA samples extracted from the oral epithelial cells were genotyped for the +1245G/T polymorphisms using real-time PCR method. RESULTS: Genotype distributions among cases and controls conformed to Hardy-Weinberg equilibrium (p = 0.2469 and p = 0.33, respectively). There was a significant difference in the genotype distribution between skiers and controls (p = 0.045, Fisher's exact test). There was no statistical difference in allele distribution: OR 1.43 (0.91-2.25), p = 0.101 (two-sided Fisher's exact test). CONCLUSIONS: The risk of ACL ruptures was around 1.43 times lower in carriers of a minor allele G as compared to carriers of the allele T.

The evaluation of function and the ultrasonographic picture of thyroid in children treated for medulloblastoma.

PURPOSE: Medulloblastoma (MB) is one of the most frequent and sensitive to radiation aggressive brain tumor in children. Abnormalities of the thyroid function are common complications of head and neck irradiation for childhood cancer. The aim of this study was to assess thyroid function in children treated for medulloblastoma according to the treatment protocol phase. PATIENTS AND METHODS: Twenty-three children with MB were enrolled to this study. All patients underwent chemotherapy and radiotherapy to the whole craniospinal axis and boost with the conformal therapy restricted to the tumor bed to a total dose of 54 Gy. Thyroid function was evaluated based on thyroid-stimulating hormone (TSH), free thyroxine (fT4) levels controlled before MB treatment, directly after irradiation and at the end of the treatment protocol. Ultrasonography has been used to detect parenchymal abnormalities. RESULTS: All patients presented normal thyroid hormone range before chemotherapy. Hypothyroidism was found in 12 patients in the course of treatment, in 2 patients hormone deficits diagnosed directly after irradiation, in 10 patients such condition was observed at the end of the whole therapy. All of these patients needed thyroid hormone substitution. None of them presented clinical symptoms of hypothyroidism. Ultrasound-detected abnormalities have been found in 20 patients. CONCLUSIONS: It is crucial to monitor the functions of the thyroid gland in children treated for medulloblastoma because of the high risk of hypothyroidism resulting from the treatment. The change in the echogenicity of the thyroid gland may be an early marker for a dysfunction of this organ in children treated for medulloblastoma.

Is the C34T polymorphism of the AMPD1 gene associated with athlete performance in rowing?

The skeletal muscle-specific isoform of adenosine monophosphate deaminase (AMPD) is one of the most important regulators of muscle energy metabolism. A nonsense C to T transition in nucleotide 34 (C34T) in exon 2 of AMPD1 gene converts the codon CAA into the premature stop-codon TAA. 127 Polish male rowers including Olympic and world champions were recruited for this study. Controls samples were obtained from 251 unrelated volunteers. Statistically significant differences in genotype distribution were observed when only a whole group of rowers (88.19% CC, 11.81% CT, 0% TT; p=0.009) were compared with controls (75.31% CC, 23.10% CT, 1,59% TT). A significant deficiency of the T allele compared to control samples was noted in the elite rowers (4.55%, p=0.021) and non-elite rowers (6.63%, p=0.023), whereas this trend was even stronger when compared with the controls for the whole group of rowers (5.91%, p=0.002). Our results suggest that the T allele is associated with physical performance level, therefore, it may be included in the group of performance altering polymorphisms as a negative factor to athletic performance.

The efficacy of radiotherapy for vertebral hemangiomas.

Vertebral hemangiomas are benign, slowly growing tumors sometimes causing local pain in the spine and/or neurologic disorders. The present paper includes 14 cases of painful vertebral hemangiomas treated by radiotherapy. All patients were irradiated using standard fractionation scheme with a total dose 20-30 Gy. One month after the treatment complete pain relief was noted in 36% of cases, five months later in 67% of cases, but in the remaining cases partial pain relief was noted. No correlation between treatment outcome and different biological and technical factors was found. No dose-response relationship was noted. The results suggest that anti-inflamatory effect of radiation plays the major role in this kind of treatment and that radiotherapy for vertebral hemangiomas is easy, short and highly effective analgetic treatment modality.

[Use of calcitonin in treatment of bone pain]. / Zastosowanie kalcytoniny w leczeniu bólu kostnego.

The studies were carried out assessing the effect of calcitonin in the treatment of bone pain. In the years 1990-1992 43 patients were studied. Pain intensity scale was used with evaluation by doctor and patient.

The GABPB1 gene A/G polymorphism in Polish rowers.

Nuclear respiratory factor 2 (NRF2), also referred to as the GA-binding protein (GABP) transcription factor, is a key transcriptional activator of many nuclear genes which encode a wide range of mitochondrial enzymes. The variants of the GABPB1 gene encoding the beta1 subunit of NRF2 protein have been associated with physical performance, particularly endurance. The aim of this study was to confirm the possible importance of the A/G polymorphism (rs7181866) in intron 3 of the GABPB1 gene in Polish rowers. The study was carried out on 55 Polish rowers and sedentary individuals, to evaluate the possible relationships between genotype and physical performance. DNA was extracted from buccal cells donated by the subjects. Genotyping was carried out by PCR-RFLP. The results revealed that the frequency of the GABPB1 A/G genotype (89.09% AA; 10.91% AG, 0% GG; vs. 97.69% AA; 2.31% AG; 0.00% GG) %; P = 0.012) and G allele (5.50% vs. 1.17%; P = 0.014) was significantly higher in the rowers compared to controls. The results suggest that the GABPB1 gene can be taken into consideration as a genetic marker in endurance athletes. However, these conclusions should be supported with more experimental studies on other GABPB1 polymorphisms and other genes in elite endurance athletes.

[Radiotherapy of vertebral hemangiomas]. / Radioterapia naczyniaków trzonów kregów przebiegajacych z objawami bólowymi.

The paper presents the analysis of results of treatment with radiotherapy of 14 cases of vertebral hemangiomas. All patients were irradiated in accordance with conventional schedule fractionated doses, using 2 Gy per fraction. The total radiation dose amounted to 20 Gy (1 case), 24 Gy (4 cases) and 30 Gy (9 cases). The degree of pain relief and lesion reossification was assessed 1 months and 6 months after completion of radiotherapy. Complete pain relief 1 month post radiotherapy was noted in 5 cases (on average patients claimed that radiotherapy resulted in a 70% decrease of pain syndromes). Six months post radiotherapy complete pain relief was noted in 8 cases (on average patients reported a 90% decrease in pain). Signs of reossification were observed in cases 6 months after treatment. No correlation was noted neither between the degree of pain relief and reossification, nor between the total delivered dose and the degree of pain relief. The obtained results allow to conclude that conventionally fractionated radiotherapy (using 20-24 Gy as total dose) is a good method of analgetic treatment of vertebral hemangiomas probably based on the anti-inflammatory effect of radiation.

[The treatment of a fracture of proximal end of the femur in own material]. / Leczenie zlaman blizszego konca kosci udowej w materiale wlasnym.

Results of treatment for fracture of proximal end of the femur in 263 patients (86 males and 177 females) aged between 7 and 104 years were analyzed. Ninety percent of the patients were older than 60 years. Mean follow-up was 4.6 years (range 1 to 9 years). Immediate Austin-Moore hip hemiarthroplasty in the elderly and screw fixation in younger patients rendered best results in the femoral neck fractures. Ender nailing in the elderly and angular plating or skeletal traction in the young proved most successful in trochanteric fractures.