The exon 3-deleted/full-length growth hormone receptor polymorphism and response to growth hormone therapy in growth hormone deficiency and Turner syndrome: a multicenter study.

BACKGROUND/AIM: The exon 3-deleted/full-length (d3/fl) growth hormone (GH) receptor (GHR) polymorphism has been associated with responsiveness to GH therapy in some diagnostic groups. However, there are still controversies on this issue. To evaluate the effect of the GHR exon 3 polymorphism on growth after 1 and 2 years of GH therapy in Turkish patients with GH deficiency (GHD) and Turner's syndrome (TS) and the distribution of GHR exon 3 isoforms. MATERIALS AND METHODS: 218 patients with GHD (125 males/93 females) and 43 patients with TS were included in the study. The control group included 477 healthy adults aged from 18 to 57 years (54 females/423 males). Anthropometric parameters and insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 were evaluated annually. GHR isoforms were studied using simple multiplex PCR. Height and body mass index were expressed as standard deviation score (SDS). RESULTS: There were no differences among TS, GHD and healthy adults regarding the distribution of GHR exon 3 isoforms (fl/fl, fl/d3 and d3/d3). There was a significant increase in height SDS in both diagnostic groups on GH therapy; however, there were neither differences in height SDS and Δheight velocity between fl/fl, fl/d3 and d3/d3 groups nor a correlation between the distribution of GHR exon 3 isoforms and change in IGF-1 SDS and IGFBP-3 SDS levels on GH therapy in either of the diagnostic groups. There was also no gender difference in GHR isoforms in healthy adults. CONCLUSION: The results suggest that responsiveness to GH therapy does not depend on the exon 3 GHR genotypes in GHD and TS patients.

The distribution of exon 3-deleted/full-length growth hormone receptor polymorphism in the Turkish population.

OBJECTIVE: The exon 3-deleted/full-length (d3/fl) growth hormone receptor (d3/fl-GHR) polymorphism has been associated with responsiveness to GH therapy in some children and also with adult height variation in the general population. We aimed to evaluate the distribution of d3/fl-GHR polymorphism in a Turkish population. METHODS: The study included 477 (54 females/423 males) healthy adults with a mean±SD age of 31.1±9.0 years (range: 18-57). Height and body mass index (BMI) were expressed as standard deviation score (SDS) according to national standards. All adults had normal height and BMI SDSs (between -2 and +2). GHR exon 3 isoforms were studied by simple multiplex polymerase chain reaction method. Insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) values were also measured and expressed as SDS. RESULTS: The distribution of the GHR exon 3 genotypes in the Turkish healthy adults was 35% (n=167) for fl/fl, 39% (n=186) for fl/d3, and 26% (n=124) for d3/d3. There was no difference between genders in GHR exon 3 genotypes. Frequencies of fl allele and d3 allele were 54.5% and 45.5%, respectively. There were no differences in height SDS and BMI SDS among the three d3/fl-GHR genotype groups. There was a significant difference in IGFBP-3 SDS between fl/fl and fl/d3 groups (p=0.022). CONCLUSIONS: This study presents the results of GHR polymorphism in a Turkish population as a reference for further studies. The distribution was similiar to European populations. There were no correlations between GHR isoforms and height SDS or other clinical/biochemical characteristics of the individuals except for higher IGFBP-3 levels in the fl/d3 group as compared to the fl/fl group. Whether this finding implies an abnormality, needs further investigation.

Reliability and validity of the Turkish version of the Memorial Symptom Assessment Scale in cancer patients.

AIM: The Memorial Symptom Assessment Scale (MSAS) is a multidimensional tool developed to evaluate measure the prevalence, characteristics and distress of common symptoms related to cancer. A validated Turkish version has now become available. The aim of this study was to evaluate its reliability and validity. METHODS: One hundred-twenty patients were included into this study. The MSAS, The Rotterdam Symptom Checklist (RSCL), and Karnofsky Performance Status Scale (KPSS) were used for data collection. Content and criterion validities were examined. Reliability analyses of the MSAS were performed using internal consistency reliability and test-retest reliability. RESULTS: The most frequently reported symptom (90%) was problems with sexual interest or activity. Item-total correlations ranged between 0.03 and 0.64. There was a high correlation between total MSAS and the RSCL (r=0.875, p<0.01). The internal consistency reliabilities of subscales of the MSAS and total MSAS were moderately high, with Cronbach alpha coefficients ranging from 0.71 to 0.84. The MSAS's test - re-test reliability was 0.78. CONCLUSION: The MSAS for cancer patients was determined to be a valid and reliable instrument for the use in the Turkish population. It is recommended that the MSAS-Turkish version can be used as a tool for comprehensive symptom assessment in planning nursing care for cancer patients.

APE1 and XRCC3 polymorphisms and myocardial infarction.

BACKGROUND: In most cells, DNA is regularly damaged by mutagens. Different DNA repair mechanisms operate on specific types of damaged DNA. When DNA damage resulting from free radicals is not repaired, it might lead to deteriorated gene expression, the development of a number of diseases such as cancer, diabetes, vascular diseases, and aging. In the present study, APE1 and XRCC3 gene polymorphisms were investigated in patients with myocardial infarction. MATERIALS AND METHODS: Forty-five first time elective coronary artery bypass grafting (CABG) patients with cardiopulmonary bypass (CPB) and 40 healthy individuals were studied. Gene polymorphisms were determined by a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: For the APE1 gene, the AG genotype was significantly higher in the patient group than in the control group. The patient group had significantly more G carriers but there was no statistically significant difference between patient and control groups the A allele. The XRCC3 TT genotype was found to be significantly more frequent in the patient group than it was in the control group. CONCLUSION: The results of our study suggested that the XRCC3 gene TT genotype and the APE1 gene AG genotype might increase the risk of myocardial infarcts.

Fas-1377 A/G polymorphism in lung cancer.

BACKGROUND: Reduced expression of Fas and/or increased expression of FasL is known to exist in some cancer types including lung cancer, so the Fas/FasL system may play a role in the course of cancer. Lack of cell surface Fas expression is one of the main routes of apoptotic resistance in tumor formation and progression. Functional mutations in the Fas gene that impair apoptotic signal transduction are associated with susceptibility to various types of cancer. In this study, we focused on lung cancer. PATIENTS AND METHODS: The genotypic tendencies that may occur due to a specific point mutation (Fas-1377 G -->A) on promoter region for Fas were evaluated. RESULTS: We did not find any relationship between Fas-1377 G-->A polymorphism and lung cancer. But there was a significantly higher number of AG patients who smoked than GG ones. CONCLUSION: There was no relationship between Fas-1377 G-->A polymorphism and lung cancer, but it was statistically significant that smoking might increase the possibility of creating lung cancer in AG genotypes more than in other genotypes.

Effects of ACE I/D polymorphism on prostate cancer risk, tumor grade and metastatis.

UNLABELLED: The aim was to substantiate the putative significance of angiotensin-converting enzyme (ACE) (insertion/deletion) I/D polymorphism on prostate cancer risk, BTPSA-A TPSA (before treatment-after treatment prostate-specific antigen) levels and tumor development. MATERIALS AND METHODS: 48 prostate cancer patients and 51 healthy volunteers were included. The ACE I/D genotypes were determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism) techniques. RESULTS: The DD genotype may have detrimental and the II genotype may have protective effect on prostate cancer (p = 0.03). The highest before treatment PSA (BTPSA) values were found in the patient group having the DD genotype (p = 0.017). PSA-AT levels were higher in homozygous mutant DD than homozygous II and the decrease in PSA-AT level was found to be statistically significant in each genotype (p = 0.000). Patients with the D allele showed a higher prevalence of late stage prostate carcinoma when compared to the patients with II genotype (p = 0.022) and the detrimental effects of the D allele, both in lymph node metastases and distant metastasis were observed. CONCLUSION: The risk of prostate cancer development, the PSA level and tumor metastasis may be associated with genetic variation in the ACE I/D genotypes which may be used as an important biomarker for further studies.

Analysis of CC chemokine receptor 5 and 2 polymorphisms and renal transplant survival.

Chronic rejection is an immune process leading to graft failure. By regulating the trafficking of leukocytes, chemokines and chemokine receptors are thought to be one of the reasons causing acute renal rejection (ARE), which increases the possibility of chronic rejection and organ destruction. This study was designed to investigate, in the Turkish population, an association of chemokine receptor genetic variants, CCR2V641, CCR5-59029-A/G, CCR5-Delta32 and acute renal rejection after renal transplant surgery. We carried out our study in 85 Turkish renal transplant patients (45 men, 40 women; mean age 39 +/- 2 years) by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. We found no significant difference in the incidence of rejection among patients possessing or lacking CCR5-Delta32. For the groups with and without acute renal rejection, we found a significant difference between the groups in A and G allele distribution in both CCR2V641and CCR559029 gene variants (p = 0.003 and p = 0.003, respectively). According to our findings, the risk of acute rejection in renal transplantation may be associated with genetic variation in the chemokine receptor genes CCR5-59029 and CCR2V641 in Turkey, and studies on these gene polymorphisms could be an ideal target for future interventions intended to prevent renal transplant loss.

C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) in meningiomas and high-grade gliomas.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) plays a role in DNA biosynthesis, methylation and repair in actively dividing cells by acting on folate metabolism. A common C677T polymorphism in the gene for MTHFR leads to an enzyme with decreased activity. MTHFR polymorphisms have been studied in various cancers but not in primary brain tumors. The purpose of this case-control study was to explore a possible association between MTHFR C677T polymorphism and primary brain tumors. MATERIALS AND METHODS: The MTHFR C677T genotype was determined in 74 patients with histologically-verified primary brain tumors and 98 cancer-free control subjects. RESULTS: The MTHFR 677T variant genotype was observed in 49% of cases and 46% of controls. Although the difference was not significant (p =0. 194), the homozygous TT genotype was found at a higher frequency in high-grade glioma (HGG) patients compared to controls (15.4% and 7.1%, respectively). The MTHFR genotype was not associated with meningioma patients. Defining patients with the CC genotype as reference, the relative risk of HGG for subjects with the T allele (CT+ TT genotype) was 1.17. CONCLUSION: In spite of the established effect of the MTHFR 677 TT genotype on DNA hypomethylation with concomitant inadequate folate levels, the MTHFR 677 TT genotype is not associated with individual susceptibility to HGG.

Paraoxonase 1 192 and 55 polymorphisms in nephrotic children.

Human paraoxonase 1 (PON1) is a serum enzyme related to high-density lipoprotein which has a major role in preventing oxidative modification of low-density lipoprotein. Due to its amino acid substitution PON1 has two genetic polymorphisms. These polymorphisms are characterized by the location of glutamine (A genotype) and arginine (B genotype) at position 192, and leucine (L genotype) and methionine (M genotype) at position 55. Hyperlipidemia and increased lipid oxidation in nephrotic syndrome may lead to glomerulosclerosis and progression of the glomerular disease. In this study we aimed to investigate PON1 192 and PON1 55 polymorphisms in children with focal segmental glomerulosclerosis (FSGS) and control subjects. The study included 25 children with biopsy-proven FSGS and 30 healthy controls. We demonstrated a statistically significant difference between FSGS patients and control subjects with respect to the distribution of the PON1 polymorphism. The AA genotype was less frequent and the AB+BB genotype was more frequent in FSGS patients than in controls (48 versus 73% for AA genotype and 52 versus 27% for AB+BB genotype, p<0.05). Distributions of PON1 55 genotypes of FSGS and control subjects were also statistically different (76 versus 43% for LL genotype and 24 versus 57% for LM+MM genotype, p<0.05) (case-control study, dominant model, Fisher's exact test). The distributions of both genotypes in subgroups of FSGS (stable renal function versus declining renal function) were not statistically different. We conclude in this preliminary study that presence of B allele and/or L allele may be risk factors for the development of FSGS in children.