Investigation of Immunovascular Polymorphisms and Intersections in Psoriasis.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease. The etiology of the disease is unknown. It is a polygenic and multifactorial disease, which interacts with genetic and environmental factors. Genetic factors (polymorphism/mutation) can alter the immune system and normal physiologically functioning keratinocytes to pathological or predisposition levels. AIMS: We aimed to investigate psoriasis at a different and novel window by searching for vascular and immunological variations and intersections in psoriasis. We investigated the main vascular and hypoxic controlling factors, which are vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 alpha (HIF-1α), as well as immunological and serotonergic factors, such as TNF-α, IL-10, and 5HT2A, which could connect each other to the pathogenesis of psoriasis. SUBJECTS AND METHODS: Nine single nucleotide polymorphisms (SNPs) in five genes were genotyped by mini-array format in 300 subjects: VEGF (rs2010963, rs833061, and rs1570360), HIF-1α (rs11549465), TNF-α (rs361525, rs1799964, and rs1800629), IL-10 (rs1800896), and 5HT2A (rs6311). RESULTS: An association was found between rs1800629 (TNF-α) and Type I psoriasis, and rs833061 (VEGF) and Type II psoriasis. Haplotype analysis suggests that the coexistence of the polymorphisms rs1799964 (TNF-α), rs2010963 (VEGF), rs833061 (VEGF), and rs6311 (5HT2A) may be a protective factor for psoriasis. CONCLUSION: Our results suggest that the vascular component of the studied vasculo-immunologic variation is more relevant in the pathogenesis of psoriasis

2004-2010

Neural tube defects (NTD) are among the most common congenital abnormalities, with an incidence of 3 per 1000 live births in Turkey. In a study of major congenital abnormalities in the city of Denizli, Turkey, abnormalities of the central nervous system are particularly common (31.1%). The objective of this study was to develop a registry of cases with NTDs in Denizli. Cases that had been diagnosed with NTD between January 2004 and September 2010 in State Hospitals of Central Denizli were retrospectively examined. The diagnoses were established based on the ICD-10 criteria. A total of 250 subjects with NTD were identified, including 123 (49.2%) females and 127 (50.8%) males with a mean age of 13.72 +/- 15.62 years (age range 1-81 years). Interestingly, spina bifida constituted a significant percentage of the cases (149 cases; 59.6%). In addition, 10 (4.0%) cases had hydrocephalus plus spina bifida. The second most common diagnosis was microcephaly, which included 70 cases (28.0%). Encephalocele was observed in only 2 cases (0.8%). Development of NTD is influenced by nutrition, socioeconomic factors, and the use of folic acid during the peri-conceptional period. Studies examining the effect of these factors on NTD in Turkey and a review of primary prevention measures are necessary

Retrospective analysis of live birth prevalence of children with Down syndrome in Denizli, Turkey.

Down syndrome (DS) is the most frequent chromosome abnormality among live births. Its prevalence increases with maternal age, and can be diagnosed by antenatal screening. We examined prevalence variations of DS in Denizli, Turkey, through a retrospective study. Sixteen years of survey data were retrieved from the two main state hospital registries from records between 1994 and 2010. We identified 113 DS live births in Denizli for 16 years. The prevalence of DS was 9.07 per 10,000 live births before the year 2000 and 9.90 after 2000. The prevalence did not change significantly. The population in Turkey is still young; the fertility rate is high in women under 35 years old and prenatal screening programs are extensively applied; for these reasons, the prevalence of DS has remained stable during these 16 years

Turkey

Oral clefts are one of the most common birth defects in humans. However, few population-based studies of these defects have been carried out in Turkey. Our objective was to determine the registries of cases of cleft lip and palate. All cases of cleft lip and palate referred to central state hospitals in Denizli between January 2000 and May 2010 were investigated retrospectively. Anomalies were determined and classified according to the ICD-10 coding system. A total of 194 cases were identified consisting of 92 females (47.4%), 100 males (51.6%), and 2 subjects of undetermined gender (1%) with an age range of 1 to 65 years. Among the 194 cases, 127 subjects (65.5%) had isolated cleft palate, including 63 females and 64 males; 42 (21.6%) subjects had cleft lip, including 17 females and 25 males; and 25 subjects (12.9%) had cleft lip and palate, including 12 females and 13 males. Studies of oral cleft prevalence are insufficient in Turkey owing to the incompleteness of registries, and the chromosome analysis rate has reached a reasonable level only in recent years

Incidence and molecular analysis of glucose-6-phosphate dehydrogenase deficiency in the province of Denizli, Turkey.

BACKGROUND: G6PD deficiency is a widespread abnormality of glucose-6-phosphate dehydrogenase, a red cell enzyme, which gives rise to hemolysis under oxidative stress. In Turkey, G6PD deficiency has a variable frequency in different regions. The prevalence and genotypes of G6PD deficiency are not known in Denizli province of the Aegean region of Turkey. Accordingly, this study was designed to investigate the prevalence of enzyme deficiency and the distribution of the Mediterranean mutation of G6PD in this region. MATERIAL/METHODS: A total of 1950 students (918 females, 1032 males, ages between 14 and 17) were screened by the Fluorescent Spot Test, and the G6PD deficiency was confirmed by quantitative spectrophotometric assay. The G6PD deficient subjects were further analyzed by the PCR/RFLP technique to identify the presence of the 563 T Mediterranean mutation. RESULTS: 24 of the subjects were found to be deficient in this enzyme, a frequency of 1.23%. Of 24 deficient subjects, 19 (79%) had the 563 T Mediterranean mutation. CONCLUSIONS: The frequency of G6PD enzyme deficiency appears to be low compared with those found in the malaria-endemic Mediterranean region of Turkey. The molecular pathology of G6PD deficiency is related to the G6PD-563 T mutation in the Denizli region

Incidence and molecular analysis of glucose-6-phosphate dehydrogenase deficiency in the province of Denizli, Turkey

Background: G6PD deficiency is a widespread abnormality of glucose-6-phosphate dehydrogenase, a red cell enzyme, which gives rise to hemolysis under oxidative stress. In Turkey, G6PD deficiency has a variable frequency in different regions. The prevalence and genotypes of G6PD deficiency are not known in Denizli province of the Aegean region of Turkey. Accordingly, this study was designed to investigate the prevalence of enzyme deficiency and the distribution of the Mediterranean mutation of G6PD in this region. Material/Methods: A total of 1950 students (918 females, 1032 males, ages between 14 and 17) were screened by the Fluorescent Spot Test, and the G6PD deficiency was confirmed by quantitative spectrophotometric assay. The G6PD deficient subjects were further analyzed by the PCR/RFLP technique to identify the presence of the 563 T Mediterranean mutation. Results: 24 of the subjects were found to be deficient in this enzyme, a frequency of 1.23%. Of 24 deficient subjects, 19 (79%) had the 563 T Mediterranean mutation. Conclusions: The frequency of G6PD enzyme deficiency appears to be low compared with those found in the malaria-endemic Mediterranean region of Turkey. The molecular pathology of G6PD deficiency is related to the G6PD-563 T mutation in the Denizli region

Bioinformatics Facilitate Haplotype Analysis in Psoriasis

Psoriasis is an inflammatory skin disease. Vitamin D is successfully used for psoriasis therapy. Polymorphisms and haplotypes in the VDR gene may explain the differences in response to vitamin D therapy. We study vitamin d receptor gene polymorphisms in 100 psoriasis patients and 100 control subjects. We have detected SNPs by PCR-RFLP and analyze by CHAPLIN. We found statistically significant allele genotype and haplotype in patients

Is Helicobacter pylori a pathogenic agent of the cervix uteri?

BACKGROUND: Helicobacter pylori is a gram-negative, microaerophilic rod-shaped bacterium that lives beneath the gastric mucosal layers, on the surface of epithelial cells. Gastric infection with this organism causes inflammation of the gastric mucosa, which can lead to gastritis, duodenal or gastric ulcers and even in rare cases to gastric carcinoma or MALT lymphoma. Approximately 50% of the population of the entire world is believed to be infected with H. pylori, but the exact route of transmission is still uncertain. It has been speculated that the cervix, with its endocervical columnar epithelium and acidic mucous layer, might provide a suitable environment for H. pylori. H. pylori might be a pathogenic agent for cervical infection. In order to address this issue we studied H. pylori in the endocervical tissue. METHODS: To investigate our hypothesis, we examined cervical tissue using PCR, culture, and Gram-stain. Thirty-three cervices from women who underwent total hysterectomy for noninvasive non-cervical benign uterine diseases were analyzed in this study. Twenty-one patients had cervicitis and 12 patients were included as controls. RESULTS: Of the 29 patients studied, none showed evidence of H. pylori infection. H. pylori was not detected by PCR, histology, or culture. CONCLUSIONS: We could not detect H. pylori in the cervix of patients with cervicitis. H. pylori-infected patients' cervices remain to be investigated, and a larger study is needed to draw firm conclusions

Vitamin D receptor gene polymorphisms and haplotypes (Apa I, Bsm I, Fok I, Taq I) in Turkish psoriasis patients.

BACKGROUND: Psoriasis is an inflammatory disease characterized by increased squamous cell proliferation and impaired differentiation. Vitamin D, Calcitriol, and its analogues are successfully used for psoriasis therapy. However, it is unknown why some psoriasis patients are resistant to Vitamin D therapy. Vitamin D mediates its activity by a nuclear receptor. It is suggested that polymorphisms and haplotypes in the VDR gene may explain the differences in response to vitamin D therapy. MATERIAL/METHODS: In this study, 102 psoriasis patients and 102 healthy controls were studied for VDR gene polymorphisms. The Fok I, Bsm I, Apa I and Taq I polymorphisms were examined by PCR-RFLP, and 50 subjects received vitamin D therapy to evaluate the association between VDR gene polymorphisms and response to vitamin D therapy. Existence of cutting site is shown by capital letters, and lack was shown by lower case. The haplotypes were analysed by CHAPLIN. RESULTS: There was significant difference in allele frequency of T and genotype frequency of Tt between cases and controls (p values 0.038 and 0.04, respectively). The Aa and bb genotypes were significantly higher in early onset than late onset psoriasis (p values 0.008 and 0.04, respectively). The genotypes Ff, ff and TT are significantly different between vitamin D3 therapy responders and non-responders (p values 0.04, 0.0001, 0.009, respectively). To the best of our knowledge, this is the first report showing importance of VDR gene haplotypes in psoriasis, the significance of the Wald and LR (Likelihood Ratio) statistics (p=0,0042) suggest that FfBbAatt is a disease-susceptibility haplotype. CONCLUSIONS: Haplotype analysis is a recent and commonly used method in genetic association studies. Our results reveal a previously unidentified susceptibility haplotype and indicate that certain haplotypes are important in the resistance to vitamin D3 therapy and the onset of psoriasis. The haplotypes can give valuable data where genotypes unable to do