A. G. Ozgen

Association of the angiotensinogen M235T and angiotensin-converting enzyme insertion/deletion gene polymorphisms in Turkish type 2 diabetic patients with and without nephropathy

OBJECTIVE Recent studies have suggested an association between a deletion variant of the angiotensin-converting enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS We investigated the relationship of the ACE insertion/deletion (I/D) and AGT M235T gene polymorphisms in Turkish patients with type 2 diabetes mellitus (DM) with and without diabetic nephropathy. A total of 102 individuals were screened for the presence of the ACE I/D and AGT M235T polymorphism: 46 individuals who had type 2 DM with diabetic nephropathy and, as controls, 56 individuals who had type 2 DM without diabetic nephropathy. Gene polymorphisms were determined by the specific melting temperature (T(m)) values of the resulting amplicons after real-time online polymerase chain reaction and melting curve analysis. RESULTS The frequencies of the ACE DD, ID, and II genotypes were 34.8%, 37.0%, and 28.3%, respectively, among type 2 diabetic patients with nephropathy, and 33.9%, 42.9%, 23.2%, respectively (P=.788), in the control subjects without diabetic nephropathy. On the other hand, the frequencies of the AGT MM, MT, and TT genotypes among the same groups were 26.1%, 52.2%, 21.7% and 26.8%, 57.1%, 16.1%, respectively (P=.758). CONCLUSIONS There were no differences in the frequencies of the AGT M235T and ACE I/D genotypes between Turkish patients with type 2 DM with and without nephropathy.

Interleukin-10 gene polymorphism in patients with papillary thyroid cancer in Turkish population

Objective: Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. Chronic inflammation has been reported to be a risk factor for thyroid neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with thyroid cancer. We aimed to evaluate the relation between the genotypic and allelic frequencies of the IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) polymorphisms, and their association with the risk of developing papillary thyroid cancer (PTC) in the Turkish population. Research design and methods: Forty-two patients with PTC and 113 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for IL-10 gene polymorphism was performed using PCR-restriction fragment length polymorphism method. Results: Statistically significant difference IL-10(-1082 G/A) gene polymorphism was determined between 2 (PTC and control) groups. No difference was determined with respect to IL-10(-592 A/C) and IL-10(-819 C/T) gene polymorphisms, and IL-10(-1082 G/A), IL-10(-592 A/C), and IL-10(-819 C/T) allele frequencies of participating between the control group and the patients with PTC (p>0.05). Conclusions: The polymorphism of IL-10(-1082 G/A) gene was significantly associated with the occurrence of PTC. Such studies will contribute significantly to our understanding of the biological role of IL-10(-1082 G/A) gene polymorphism in PTC development. In conclusion, IL-10(-1082 G/A) gene polymorphism may affect the survival of papillary thyroid carcinoma.

The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy

Poor glycaemic control, hypertension and duration of diabetes are risk factors for the development of diabetic nephropathy, but there may be genetic factors. Recently, a common C to T mutation at nucleotide position 677 of the MTHFR gene (MTHFR677C > T) has been reported to be correlated with hyperhomocysteinemia and the severity of coronary artery disease as macroangiopathy. We aim to investigate Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy group and examine the contribution of the MTHFR gene polymorphism to the development of diabetic nephropathy.

Fas/Fas ligand gene polymorphism in patients with papillary thyroid cancer in the Turkish population.

Objective: Fas ligand (FasL) is an apoptotic agent and a member of tumor necrosis factor (TNF) family. FasL exists in cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, and it is increased in tumor cell membrane. On the contrary, CTL and NK are bound to Fas on the surfaces of cell membrane; this triggers apoptosis in cytotoxic cells and leads to their death. This system plays an important role in eliminating viral infections and cancer cells. Malfunction of this system results in the development and spread of the malignancy. This study aims at evaluating the influence of Fas and FasL gene polymorphism in papillary thyroid cancer (PTC) in the Turkish population. Research design and methods: Forty-five patients with PTC and 100 healthy controls were included in this study. The diagnosis of PTC was confirmed by histopathologic examination after surgery. The evaluation of genotype for Fas 670 A/G and FasL 843 C/T gene polymorphism was performed using the PCR-restriction fragment length polymorphism (RFLP) method. Results: The evaluation of Fas/FasL genotype and gene allele frequency did not show statistically significant differences between the patient and control group (p>0.05). In addition, the univariate analysis did not reveal a statistically significant relationship between the size of the nodule and the Fas/FasL gene polymorphism in patients with PTC. Conclusions: As in other types of malignancy, genetic factors in the pathogenesis of PTC may also show changes in different populations. Fas/FasL gene polymorphysms are possible that different mechanisms function in apoptosis balance in PTC development.

Interleukin-10 (-1082G/A) Gene Polymorphism in Patients With Type 2 Diabetes With and Without Nephropathy

OBJECTIVE Interleukin (IL)-10 is a major anti-inflammatory cytokine that plays a crucial role in the regulation of the immune system. IL-10 has met the criteria for an anti-inflammatory and an immunosuppressive cytokine, its activity may be important for clinical outcome of diabetic nephropathy (DN). We aimed at evaluating the relation between the genotypic and allelic frequencies of the IL-10 (-1082G/A) polymorphisms, and their association with the risk to develop DN in the Turkish population. RESEARCH DESIGN AND METHODS The (IL)-10 (-1082G/A) genotypes were retrospectively determined in 43 patients with nephropathy and 48 without nephropathy and a control group of 112 healthy individuals. The polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism. RESULTS This genotype distribution was different between control subjects and patients with type 2 diabetes in which 24.2% were AA, 75.8% were GA, and 0% were GG (p<0.001). The frequency of the mutant G allele was 36.1% in patients with diabetes nephropathy versus 39.6% in those without nephropathy (p>0.05). The genotype frequencies were AA, 27.9%; GA, 72.1%; and GG, 0% in patients with diabetes with nephropathy versus AA, 20.8%; GA, 79.2%; and GG, 0% in those without nephropathy (p>0.05). CONCLUSIONS The polymorphisms of IL-10 (-1082G/A) genes were significantly associated with the occurrence of patients with type 2 diabetes. The IL-10 (-1082G/A) genotype and allele frequencies were not different between patients with diabetes with nephropathy and those without nephropathy. Therefore, we conclude that the IL-10 (-1082G/A) gene polymorphism is not associated with the development of DN in Turkish patients with type 2 diabetes.

Increasing severity of cardiac autonomic neuropathy is associated with increasing prevalence of nephropathy, retinopathy, and peripheral neuropathy in Turkish type 2 diabetics.

BACKGROUND Cardiac autonomic neuropathy (CAN) is the most frequent and clinically important form of diabetic autonomic neuropathy. CAN is associated with increased frequency of other microvascular complications of diabetes mellitus (DM). In this study, we evaluated the prevalence diabetic nephropathy, retinopathy, and peripheral neuropathy, and measured gastric emptying time and bladder emptying time in type 2 diabetic patients with varying degrees of CAN. PATIENTS AND METHODS Fifty-three patients with DM complicated by CAN (30 women and 23 men; mean age, 58.8+/-9.15 years; duration of diabetes, 13.9+/-7.7 years) were included in this study. The patients were grouped according to the degree of CAN as early, definite, and severe CAN. RESULTS There were significant differences regarding the prevalence of nephropathy, retinopathy, and peripheral neuropathy diagnosed by EMG among those groups (P<.05). However, there was no significant difference regarding the prevalence of peripheral neuropathy diagnosed by neurological examination (P>.05), and scintigraphic measurements of gastric and bladder emptying time were comparable among the groups (P>.05). CONCLUSION The prevalence of other diabetic microvascular complications increase as the severity of CAN increases in patients with type 2 DM. This study emphasizes the need for an early screening for peripheral neuropathy, retinopathy, and nephropathy in type 2 diabetic patients with CAN, especially with severe involvement.

The (-174) G/C polymorphism in the interleukin-6 gene is associated with risk of papillary thyroid carcinoma in Turkish patients

Introduction: Interleukins and cytokines play an important role in the pathogenesis of many cancers. We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in patients with papillary thyroid carcinoma (PTC) and control subjects. Material and methods: In this study, 42 patients with PTC and 340 healthy controls were included. Peripheral blood samples were taken from control group and patients, and blood samples were preserved at −80 C in tubes containing Na-EDTA. Results: We also found a statistically significant difference between patients with PTC and the control group with respect to IL-6 genotype (p<0.05). IL-6 gene polymorphism in patients with PTC patients did not reveal statistically significant difference between the 2 groups (size of tumor >1 cm and <1 cm), multicentricity, RET-PTC types and capsule invasion (p>0.05). We also did not find a statistically significant difference between patients with PTC and the control group with respect to IL-6-gene allele frequency (p>0.05). Discussion: Our data suggest that the IL-6 G-174 C polymorphism could play a role in thyroid cancer risk, but there is no effective role as a prognostic factor.

Effect Of G2706A and G1051A polymorphisms of the ABCA1 gene on the lipid, oxidative stress and homocystein levels in Turkish patients with polycystıc ovary syndrome

BackgroundObesity, insulin resistance and hyperandrogenism, crucial parameters of Polycystic ovary syndrome (PCOS) play significant pathophysiological roles in lipidemic aberrations associated within the syndrome. Parts of the metabolic syndrome (low HDL and insulin resistance) appeared to facilitate the association between PCOS and coronary artery disease, independently of obesity. ABCA1 gene polymorphism may be altered this components in PCOS patients.In this study, we studied 98 PCOS patients and 93 healthy controls. All subjects underwent venous blood drawing for complete hormonal assays, lipid profile, glucose, insulin, malondialdehyde, nitric oxide, disulfide levels and ABCA genetic study.ResultsIn PCOS group fasting glucose, DHEAS, 17-OHP, free testosterone, total-cholesterol, triglyceride, LDL-cholesterol and fibrinogen were significantly different compare to controls. The genotype ABCA G2706A distribution differed between the control group (GG 60.7%, GA 32.1%, AA 7.1%) and the PCOS patients (GG 8.7%, GA 8.7%, AA 76.8%). The frequency of the A allele (ABCAG2706A) was higher in PCOS patients than control group with 13,0% and 23,2%, respectively. In this study, the homocystein and insulin levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.ConclusionsWe found higher percentage of AA genotype and A allele of ABCA G2706A in PCOS patients compare to controls. The fasting insulin and homocystein levels were significantly higher in PCOS patients with ABCA G1051A mutant genotype than those with heterozygote and wild genotypes.

US findings in euthyroid patients with positive antithyroid autoantibody tests compared to normal and hypothyroid cases.

PURPOSE We aimed to compare the ultrasonographic and laboratory parameters of euthyroid patients who have only positive antithyroid autoantibody test results with those of patients with a hypothyroid status of Hashimotos thyroiditis (HT). MATERIALS AND METHODS Thirty-five patients with newly diagnosed HT, 35 euthyroid patients who have autoantibodies against thyroid peroxidase (TPOAb) and/or thyroglobulin (TgAb), and 40 controls were enrolled in the study. Plasma free T3, free T4, thyroid stimulating hormone, TPOAb, and TgAb levels were obtained retrospectively. For gray-scale ultrasonography, each thyroid gland of all individuals graded with gray-scale grading (GSG), which was determined according to the gland size, parenchymal structure, echogenicity, micronodulation, contour irregularity, and existence of hyperechoic septa. For Doppler analysis, the peak systolic velocity (S), resistive index (RI), and pulsatility index (PI) values were obtained from the superior thyroid artery (STA) and intrathyroidal artery (ITA). The color pixel ratio (CPR), which was computationally evaluated from a power Doppler image of all individuals, was used for quantification of the intrathyroidal vascularity. RESULTS Although the mean GSG values were higher in the HT and antibody-positive groups than they were in the control group, there was no significant difference between the HT and antibody-positive groups. The three study groups demonstrated no statistically significant difference with regard to the S, RI, or PI variables obtained from the STAs and ITAs. Although the CPR values were highest in the HT group, the difference between the HT and antibody-positive group did not reach statistical significance. CONCLUSION The euthyroid antibody-positive group revealed gray-scale and Doppler ultrasonographic findings that were similar to those of the HT group.

Occurrence of Riedel’s Thyroiditis in the course of sub-acute thyroiditis

Riedel’s Thyroiditis is an uncommon form of chronic thyroiditis characterized by an invasive fibrosclerosis of the gland, often involving surrounding tissue. The relationship of Riedel’s Thyroiditis to other forms of thyroiditis is not clear. We presented a 47 year-old woman first diagnosed with sub-acute thyroiditis based on clinical findings and laboratory results. Eight months later, she had a thyroidectomy operation due to an enlargement of the thyroid gland and symptoms of compression. Histopathologic evaluation showed that she had Riedel’s Thyroiditis, but there were some histopathologic findings of sub-acute thyroiditis as well. Until now, there has only been one case reported in which Riedel’s Thyroiditis was diagnosed in a patient with a history of sub-acute thyroiditis in the literature. Although aetiology of Riedel’s Thyroiditis is unknown, it may develop in the course of sub-acute thyroiditis.