IGF(CA)19 and IGFBP-3-202A/C gene polymorphism in patients with acromegaly.

OBJECTIVE: We aimed to investigate IGF-1 and IGFBP-3 gene polymorphisms in patients with acromegaly. DESIGN: We included 34 patients with acromegaly and 37 healthy subjects to study. At baseline examinations, antropometric measurements were done. Genomic DNA from the patients and controls were prepared. Serum, glucose, insulin, total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, growth hormone (GH), Insulin-like growth factor I (IGF-I) and IGFBP-3 levels of subjects were analyzed. RESULTS: The frequency of genotype IGF-1(CA)19 and IGFBP3-202 A/C gene was significantly different between control and patients. In acromegalic patients, a significant difference in the serum IGF-1 levels and LDL cholesterol levels among the three IGF(CA)19 genotype. LDL levels were positively correlated with IGF-1. Subjects having >194 bp genotype had higher IGF-1 and LDL cholesterol levels. We observed that the patients with 194 bp genotype have more invasive and bigger tumors and they require adjunctive therapies. Clinical characteristics among the three IGFBP3-202 A/C genotype, AA, AC and CC, did not display any significant difference. CONCLUSIONS: In our study, 194 bp allele (20 CA repeats) of the IGF-I promoter have higher circulating IGF-I levels than others. We have found that the patients with 194 bp genotype are the resistant patients with active disease and they required high dose medication. We think this study may help to define the patients, who are resistant to drug therapy, and possible cardiovascular disease.

Angiotensin-converting enzyme gene polymorphism in overweight and obese Turkish patients with insulin resistance.

The aim of this study was to analyze the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in obese Turkish patients with insulin resistance (IR). Sixty-two obese Turkish patients with IR were enrolled in this study. One hundred healthy people without IR were recruited as the control group. ACE amplification was performed by polymerase chain reaction. The frequency of the DD genotype was significantly higher in obese patients with IR than in control subjects. Of sixty-two patients, 1 (1.6%) had an II genotype, 22 (35.5%) had an ID genotype, and 39 (62.9%) had a DD genotype. The frequency of the I allele in the patient group was significantly lower than in controls. We found that the frequency of the DD genotype was higher in obese Turkish patients with IR. ACE gene I/D polymorphism may be associated with obesity in the Turkish population.

IGF-1 gene polymorphism in obese patients with insulin resistance.

IGFs (Insulin like growth factors) are important regulators of pancreatic beta cell development, growth and maintenance. Mutations in the IGF genes have been found to be associated with diabetes mellitus, myocardial infarction obesity. These associations could result from changes in insulin secretion. We aimed to investigate IGF-1 gene polymorphism in obese patients with insulin resistance. We included 100 obese patients with insulin resistance 30 healthy subjects to study. At baseline examinations, antropometric measurements were done. Genomic DNA from the patients and controls were prepared. Thyroid function tests and serum IGFBP3 levels were similar between patients and controls whereas IGF, GH levels were significantly lower in obese patients. We categorized the IGF-1 (CA)19 polymorphism area into 3 groups as lower than 192 bp (group 1), 192-194 bp (group 2), and higher than 194 bp(group 3). Group 3 was more frequent in both obese and control groups. IGF-1 levels were also significantly lower in obese group (138.51 +/- 49.3) in than controls (218.14 +/- 69.15). IGF-1 levels were significantly lower in obese patients. The most frequent IGF-1 gen polymorphism allel is >194 bp in both obese insulin resistant patients and controls. IGF-1 levels and the other biochemical and hormonal parameters were similar in different genotype groups. The cause of lower IGF-1 levels in obese patients might be different from IGF-1 gene polymorphism and it may be insulin resistance.

Association of MDR1 C3435T polymorphism with bipolar disorder in patients treated with valproic acid.

P-glycoprotein (P-gp), an efflux transporter protein, is an ABC transporter encoded by the multidrug resistance 1 gene (MDR1, ABCB1). The common synonymous C3435T polymorphism in exon 26 is reported to associate with lower P-gp functional expression and drug uptake. Many extended pharmacogenomics, functional, and complex disease association studies focused mainly on this polymorphism. We investigated the association of exon 26 C3435T genetic variants of MDR1 gene with susceptibility to bipolar disorder and serum valproic acid concentration. Totally, 104 patients meeting DSM-IV criteria for bipolar disorder and 169 controls were admitted to the study. There was statistically significant difference between the genotypes of bipolar patients (CT 91.2%, TT 6.8%, and CC 2%) and controls (CT 52.7%, TT 26%, CC 21.3%) although their allelic distribution was similar. The serum valproic acid concentrations of the patients with CT, TT and CC genotypes were 72.92 +/- 20.55, 80.47 +/- 14.01 and 68.29 +/- 12.17 microg/ml, respectively, and there was no significant difference between the C3435T genotypes.

Insulin-like growth factor-I gene and insulin-like growth factor binding protein-3 polymorphism in patients with thyroid dysfunction.

BACKGROUND AND AIMS: Thyroid hormones have important roles in normal growth and skeletal muscle development. IGF-I is one of the most important growth factors and is needed for the proliferation and development of thyroid cells. It stimulates fibroblasts, follicular and endothelia cells in thyroid gland. It has been shown that thyroid hormones play an important role in the regulation of IGF-I and IGFBP-3. In this study we proposed that IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphism may affect thyroid functions. For this purpose, frequency of IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphism in hypo- and hyperthyroid patients and possible role of these polymorphism in thyroid functions were investigated. METHODS: This study was performed on 37 volunteer hyperthyroid and 76 hypothyroid patients as well as with 50 healthy subjects as controls. DNA isolation was applied in peripheral blood samples obtained from patients and controls. Required areas were amplified with PCR by using proper primers belonging to these gene areas from the isolated DNA samples. The products were evaluated with visualization by UV gel documentation system. RESULTS: Frequency of IGF-I (CA)(19) gene polymorphism among hypothyroidism patients, hyperthyroidism patients and controls were statistically significant (chi(2) = 11.55, df = 4, p = 0.021). Genotypic variations between hyper- and hypothyroid patients were significant (chi(2) = 11.39, df = 2, p = 0.003), whereas there was no difference in IGF-I (CA)(19) gene polymorphism between the patients and controls. Differences in the IGFBP-3-202 A/C gene polymorphism between controls and hypo- as well as hyperthyroid patients were not significant. But IGFBP-3-202 A/C gene polymorphism genotype frequencies showed a significant difference between hypo- and hyperthyroid patients (chi(2) = 6.24, df = 2, p = 0.044). CONCLUSIONS: These findings suggests that IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphisms may be a risk factor for hypothyroidism.

Influence of classical and rock music on red blood cell rheological properties in rats.

BACKGROUND: A number of studies have reported physiological effects of music. Different types of music have been found to induce different alterations. Although some physiological and psychological parameters have been demonstrated to be influenced by music, the effect of music on hemorheological parameters such as red blood cell (RBC) deformability and aggregation are unknown. This study aimed at investigating the effects of classical and rock music on hemorheological parameters in rats. MATERIAL/METHODS: Twenty-eight rats were divided into four groups: the control, noise-applied, and the classical music- and rock music-applied groups. Taped classical or rock music were played repeatedly for 1 hour a day for 2 weeks and 95-dB machine sound was applied to the noise-applied rats during the same period. RBC deformability and aggregation were measured using an ektacytometer. RESULTS: RBC deformability was found to be increased in the classical music group. Exposure to both classical and rock music resulted in a decrement in erythrocyte aggregation, but the decline in RBC aggregation was of a higher degree of significance in the classical music group. Exposure to noise did not have any effect on the parameters studied. CONCLUSIONS: The results of this study indicate that the alterations in hemorheological parameters were more pronounced in the classical music group compared with the rock music group.

P-glycoprotein polymorphism in hypo- and hyper-thyroidism patients.

P-glycoprotein (Pgp) is encoded by the multidrug resistance gene (MDR1) in humans and is the product of MDR1. It is expressed in various tissues and is related to drug distribution in intestinal erythrocytes, capillary endotel of brain, proximal tubules cells of kidneys and liver canalicular cells. Expression of Pgp is affected by Pgp polymorphism, and exon 26 C3435T polymorphism is the most common one. It has been thought that expression of Pgp is high in C-allele subjects and this situation is responsible for the resistance against some drugs and substances. Pgp may have a role in the distribution of thyroid hormones, drugs used for hypo- and hyperthyroidism and the resistance occurred. For this purpose possible relationship between T and C alleles and frequency of Pgp polymorphism as well as thyroid hormone distribution in patients with hypo- and hyperthyroidism was investigated. Thirty five hyperthyroidism patients diagnosed as Graves' disease, 78 hypothyroidism patients diagnosed as Hashimoto's thyroiditis and 100 healthy volunteers were included in the study. According to the results obtained no statistically significant difference was found in Pgp C3435T polymorphism between hypo- and hyperthyroidism patients. In addition, the serum free T3 levels of hyperthyroidism patients with C alleles was higher than those of subjects with T alleles. No statistically significant difference was seen in the CC, CT and TT genotype frequencies between the patients and control groups. In conclusion, it seems that Pgp polymorphism is not a predictor factor for the occurrence of hypo- and hyperthyroidism. There is a significant relationship between Pgp and the elevated serum free T3 levels of hyperthyroidism patients, and further research will help understand this situation.

Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors.

The aims of the present study were to investigate the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in breast cancer patients and the association between ACE genotypes and clinicopathologic features, as well as their effects on prognosis. We assessed the I/D polymophism of the ACE gene by using polymerase chain reaction from peripheral blood in breast cancer and healthy age-matched women. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Of the 57 patients, 31 (54.4%) had DD, 24 (42.1%) had ID, and 2 (3.5%) had II genotypes. In control subjects, 33 (63.5%) had DD, 12 (23.1%) had ID, and 7 (13.4%) had II genotypes. The ID genotype was seen more commonly in breast cancer patients (p = .03). When the combination of ID and II genotypes was used as a reference group, the DD genotype was associated with negative hormone receptor status (p = .003), tumor size (p = .054), and lymph node involvement (p = .07) but not histologic high grade and c-erb B2 overexpression. These results suggest that the DD genotype may accompany poor prognostic factors and influence the tumor course.

MDR1 C3435T polymorphism in patients with breast cancer.

BACKGROUND: The human multidrug-resistant gene (MDR1) encodes P-glycoprotein (Pgp), a membrane-bound efflux transporter conferring resistance to a number of natural cytotoxic drugs and potentially toxic xenobiotics. Single-nucleotide polymorphisms (SNPs) in MDR1 gene are associated with phenotypic variation in Pgp expression levels of tissue. SNPs may alter the physiological protective role of Pgp and, therefore, influence disease risk. METHODS: In our study we identified the MDR1 C3435T polymorphism in breast cancer patients (n = 57) and healthy subjects (n = 50). DNA was extracted from peripheral blood samples by standard phenol/chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of C3435T single nucleotide polymorphism. RESULTS: We obtained CC, CT and TT genotype frequencies in breast cancer patients as 12.3%, 57.9% and 29.8%, respectively. In the control group, frequencies of genotypes were found as 36% for CC, 46% for CT and 18% for TT. We observed difference in SNPs in MDR1 gene C3435T polymorphism between breast cancer patients and healthy controls (chi(2) = 8.66, df = 2, p = 0.013). The C allele frequency was found in 41.2% and the T allele frequency was found in 58.8%. C3435T MDR1 gene allele frequencies in breast cancer patients as compared to results in control group were as follows: [OR = 1.5 (95% CI: 1.09-1.96)]. In the patient group, T allele frequency was significantly higher than controls (p <0.01). Clinicopathological parameters of patients with breast cancer were compared for C3435T polymorphism. We did not find any significant difference between clinicopathological parameters and MDR1 phenotype of breast cancer patients. The progression-free survival rate in a subgroup analysis based on MDR1 genotypes with CC genotype was 71.4%, CT genotype was 75.7%, and TT genotype was 88.2%, respectively. This difference was not statistically significant (log rank p = 0.63). CONCLUSIONS: Results of the present study demonstrated a 1.5-fold increased risk for development of breast cancer in T allele carriers.

Association between the polymorphism of the angiotensin-converting enzyme gene and tumor size of breast cancer in premenopausal patients.

The association between the polymorphism of the angiotensin-converting enzyme (ACE) gene and breast cancer risk has been extensively studied, however, the studies about the prognostic factors and ACE gene polymorphism are limited in number. Our aims were to analyze the distribution of the insertion/deletion (I/D) polymorphism of the ACE gene in Turkish premenopausal patients with breast cancer, which is more aggressive than the postmenopausal counterpart, and to assess whether DD genotype is associated with poor prognostic factors. The DD genotype has been shown to be associated with the increased serum and tissue levels of ACE, compared to those in II and ID genotypes. ACE genotypes were determined by polymerase chain reaction in 44 Turkish premenopausal patients with breast cancer and in 46 age-matched healthy premenopausal women. ACE genotypes are distributed in patients and control subjects as follows; DD is present in 25 (56.8%), ID in 17 (38.6%), and II in 2 (4.5%) patients, and DD in 28 (60.9%), ID in 12 (26.1%), and II in 6 (13.0%) healthy subjects, respectively. D and I alleles were found in 76.1% and 23.9% of the patients, while 73.9% and 26.1% in healthy subjects, respectively. In breast cancer patients, no significant association was observed between the ACE genotypes and poor prognostic factors, such as negative hormone receptor status, histological grade, lymph node involvement, higher number of lymph node metastases, and c-erb B2 overexpression, except that tumor size greater than 2 cm is associated with DD genotype (p = 0.02). Thus, ACE may influence the local tumor growth of breast cancer in premenopausal patients.