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.

Effects of myeloperoxidase -463 G/A gene polymorphism and plasma levels on coronary artery disease.

Myeloperoxidase is a lysosomal enzyme of polymorphonuclear leucocytes that contributes to inflammatory responses. In previous studies it was shown that MPO was synthesized in atherosclerotic lesions responsible of lipoprotein oxidations. We aimed to determine the MPO -463 G/A gene polymorphism distribution in Turkish population and evaluate the effects of it on myeloperoxidase levels. There were 100 myocardial infarct patients and 100 healthy control subjects in our study. MPO polymorphism was studied by using PCR-RFLP technique and MPO levels were measured by ELISA. It was shown that MPO levels were increasing in patients after myocardial infarct event but there were no effect of MPO -463 G/A polymorphism on MPO levels. It was also found that serum total cholesterol and LDL-cholesterol levels and smoking was contributing factors in increments of MPO enzymes. We observed that MPO levels were increased in CAD but there were no effect of MPO -463 G/A polymorphism on MPO levels.

Comparison of lipid profiles in relation to APOB EcoRI polymorphism in obese children with hyperlipidemia.

BACKGROUND: We aimed to evaluate apolipoprotein B-100 (APOB) EcoRI polymorphism and plasma lipid parameters together in children and adolescents. This is the first such study in Turkey to determine possible relationships of these parameters. MATERIALS AND METHODS: Three separate groups were studied: a group of obese children with hyperlipidemia, a group of obese children without hyperlipidemia, and a group of healthy children neither with hyperlipidemia nor obesity. Polymerase chain reaction (PCR), denaturating gradient gel electrophoresis (DGGE) and automatic sequence analysis techniques were used. Sequencing results were examined by Proseq and BioEdit computer programmes. RESULTS: Mutant A allele was not observed in the healthy control group, whereas it was more frequent in the hyperlipidemic obese children; the GA genotype was correlated with total and low density lipoprotein-cholesterol levels. CONCLUSION: In this study, we suggest that obese child patients having the A allele could have a higher risk for developing hyperlipidemia.

Bladder cancer and polymorphisms of DNA repair genes (XRCC1, XRCC3, XPD, XPG, APE1, hOGG1).

Carcinogenic molecules from cigarettes are known to cause DNA damage to bladder epithelial cells, but such damage can be corrected by some DNA repair mechanisms such as base and nucleotide excision repair, double-strand repair and mismatch repair. Various gene products play a role in these DNA repair systems. The aim of this study was to investigate six of these genes (XRCC1, XRCC3, XPD, XPG, APE1, hOGG1) each of which has a separate role in these repair mechanisms. The study was performed on 83 bladder cancer patients and 45 healthy controls. The genes were amplified by polymerase chain reaction (PCR) and restriction fragment polymorphism determinations were used to elucidate the specific changes in the gene region. There was no difference in smoking status between patient and control groups. It was found that there was a statistical significance in XRCC3 T carriers between patient and control groups and so there was a 4.87-fold protective role by the XRCC3 T allele against bladder cancer. The AA genotype and A allele carriers of the APE gene were more frequent in the transitional epithelial carcinoma group than in the adenocarcinoma group. The genotype distribution for the APE gene was determined to be significantly different between local and invasive cases; G allele carriers for this gene were significantly higher in invasive cancer types.

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.

Effects of manganase superoxide dismutase Ala-9Val polymorphism on prostate cancer: a case-control study.

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a major enzyme that is responsible for the detoxification of reactive oxygen species in the mitochondria. Mitochondrial DNA damage may contribute to carcinogenesis as an important risk factor. The aim of this study was to investigate the relationship between prostate cancer and MnSOD Ala-9Val polymorphism in Turkish men with prostate cancer. PATIENTS AND METHODS: Fifty patients with prostate cancer and 50 healthy controls were included in this study. Gene polymorphism was determined using a PCR-RFLP method. RESULTS: The Ala/Ala genotype and the Ala allele were found at statistically higher frequencies in patients with prostate cancer as compared to controls (p < 0.05). The patients suffering from prostate cancer were divided into two groups according to Gleason score: aggressive prostate cancer and non-aggressive prostate cancer. It was observed that carrying the Ala/Ala genotype or the Ala allele resulted in an insignificant increase in the frequency of aggressive prostate cancer compared to nonaggressive prostate cancer. It was concluded that MnSOD Ala allele might be the cause of prostate cancer risk among alcohol users. CONCLUSION: The results of our study of Turkish prostate cancer patients suggest that mutation of the MnSOD gene may be an important risk factor for prostate cancer.