The Relationship Between Sexual Dysfunctions With Disease Prolactin and Genetic Polymorphisms in Schizophrenia and Bipolar Disorder Patients Receiving Pharmacotherapy.

OBJECTIVE: The aim of this study is to investigate sexual dysfunctions (SDs) and related factors in patients with schizophrenia and bipolar disorder receiving pharmacotherapy. METHODS: This study included 111 patients. The Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Calgary Depression Scale for Schizophrenia (CDSS) were applied to the schizophrenia, and the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) to the bipolar patient group. The sociodemographic data form and the Arizona Sexual Experiences Scale (ASEX) were applied to both of the patient groups. Blood was drawn from all patients to evaluate the indicated gene polymorphisms and evaluate prolactin levels. RESULTS: SD was detected in 45.9% (N = 34) of the schizophrenia group, and 59.5% (N = 22) in the bipolar disorder group. SD was significantly higher in elderly patients and patients with a high smoking amount and low education levels. The eNOS -786T>C T allele frequency was found to be significantly higher in patients with SD. The logistic regression analysis determined that eNOS -786T>C CT and TT genotypes increased the risk of SD. CONCLUSION: In this study, the high rates of SD in patients with schizophrenia and bipolar disorder, and the presence of modifiable factors that influence the presence of SD, suggest that SD should be given more attention in these patient groups. On the other hand, the high rate of SD in patients with the eNOS -786T>C T allele indicates the importance of carrying out new studies investigating the factors affecting the enzyme activity in this genotype. There is a need for more studies on eNOS genotypes and enzyme activites in this area.

IL-23R gene polymorphisms in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common autoimmune disease in which many different genetic variants of functional gene polymorphisms may play a culprit role in the underlying pathogenetic mechanism. The recent studies suggest that interleukin-23 receptor (IL-23R) gene polymorphisms may increase susceptibility to the development of various autoimmune diseases. We aimed to examine the possible relationship of nine single nucleotide polymorphisms (SNPs) in the IL-23R gene to susceptibility to rheumatoid arthritis and their associations with disease characteristics in the South Aegean region of Turkey. We enrolled 100 rheumatoid arthritis patients and age- and sex-matched 96 healthy subjects in the study. After deoxyribonucleic acid (DNA) isolation was performed, a 'Restriction Fragment Length Polymorphism' (RFLP) method was used for the investigation of polymorphisms associated with the IL-23R gene. Allele identification and genotyping were obtained from polymerase chain reaction (PCR) products using gel electrophoresis. Allele frequencies and detected genotypes were compared between groups. All statistical analyses were performed using SPSS 25.0 (IBM SPSS Statistics 25 software (Armonk, NY: IBM Corp.)). Continuous variables were defined by the mean ± standard deviation and categorical variables were defined by number and percent. Logistic Regression Analysis was used for determining which variables affect the presence of RA. Differences between categorical variables were analyzed with Chi-square analysis. Statistical significance was determined as p < 0.05. The mean age was 53.48 ± 11.7 years in the RA group, whereas 52.55 ± 12.7 years in the healthy control group. The genotypes of IL-23R with rs11805303(TT), rs10889677(AA), rs1004819(AA), and rs7530511(CT) polymorphisms were seen more often in RA patients than healthy controls. Having the AA genotype of IL-23R rs1004819 and the CT genotype of Il-23R rs7530511 increase the development risk of RA with a statistical significance (OR: 3.416 p = 0.003 and OR: 4.899 p = 0.0001, respectively). RA patients with the CC genotype of Il-23R with rs11805303, the CC genotype with rs10889677, and the TT genotype with rs2201841 of the IL-23R gene had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels than with other genotypes. RA patients with the CC genotype rs11805303 and the GG genotype rs1004819 of the IL-23R gene had more active disease. Our findings suggest that all of the nine analyzed IL-23R gene polymorphisms are seen more frequently than healthy controls in our study population. Besides, some SNPs were related to higher acute phase reactants and higher disease activity scores.

The miRNA content of circulating exosomes in DLBCL patients and in vitro influence of DLBCL-derived exosomes on miRNA expression of healthy B-cells from peripheral blood.

BACKGROUND: Due to the heterogeneous nature of Diffuse Large B-cell Lymphoma (DLBCL), the mechanisms underlying tumor development and progression have not yet been fully elucidated. OBJECTIVE: This study aimed to compare the characteristics of plasma exosomes of DLBCL patients and healthy individuals and to evaluate the exosomal interactions between DLBCL cell lines and normal B-cells. METHODS: Exosome isolation was performed using an ultracentrifugation-based protocol from plasma of 20 patients with DLBCL and 20 controls. The expression of miRNAs from exosome samples was analyzed using a miRNA expression microarray. The presence of exosome-mediated communication between the lymphoma cells and normal B-cells was determined by the co-culture model. RESULTS: A significant increase in plasma exosome concentrations of DLBCL patients was observed. There was also a significant decrease in the expression of 33 miRNAs in plasma exosomes of DLBCL patients. It was determined that normal B-cells internalize DLBCL-derived exosomes and then miRNA expression differences observed in normal B-cells are specific to lymphoma-subtypes. CONCLUSIONS: MiR-3960, miR-6089 and miR-939-5p can be used as the miRNA signature in DLBCL diagnosis. We suppose that the exosomes changed the molecular signature of the target cells depending on the genomic characterization of the lymphoma cells they have originated.

Relationship of Plasminogen Activator Inhibitor 1 4G/5G Gene Polymorphism and Nontraumatic Lunatum Avascular Necrosis.

PURPOSE: Plasminogen activator inhibitor 1 (PAI-1) is a critical enzyme that regulates coagulation and fibrinolytic systems. The aim of this study was to determine the role of PAI-1 4G/5G polymorphism in nontraumatic avascular necrosis of the lunate. METHODS: The study included 45 patients with Kienböck disease and 45 healthy individuals as a control group. In both groups, genomic DNA was extracted from peripheral blood samples to determine the distributions of PAI-1 4G/5G polymorphism using allele-specific polymerase chain reaction and sequencing. RESULTS: No statistically significant difference was determined in the distribution of the gene polymorphism between the patient and control groups. We found the 5G/5G genotype to be 1.7 times higher in the control group compared with the patient group. A 1.6-fold increase in the 4G homozygote genotype was identified in the patient group. The patient and control groups were also evaluated for 4G/4G plus 4G/5G and 5G/5G in terms of genotype distribution. No statistically significant difference was found. CONCLUSIONS: The findings suggest that the PAI-1 4G/4G polymorphism is not a genetic risk for Kienböck disease. CLINICAL RELEVANCE: This study aimed to reveal the genetic etiology of Kienböck disease.

Altered microRNA 5692b and microRNA let-7d expression levels in children and adolescents with attention deficit hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Its etiology is not clearly understood yet, but neurobiological, genetic and environmental factors are shown to play a role. The relationship between ADHD and miRNAs has been studied quite recently, and few studies have been conducted up to now. In this study, peripheral blood expression levels of miR-5692b, miR-let-7d, miR-124-3p, miR-4447 and miR-107 of 30 children and adolescents with combined type ADHD were compared to 30 healthy controls to understand the roles of these miRNAs in the ADHD etiopathogenesis. Compared to controls, levels of miR-5692b (p = 0.006) were found higher and levels of miR-let-7d (p = 0.017) were found lower in the ADHD group. There was no significant difference in terms of miR-124-3p, miR-4447, and miR-107 levels between the groups. In conclusion, our findings support other studies suggesting the importance of miRNAs in the pathogenesis of ADHD. Regarding the regulatory role of miRNAs in gene regulation, their contribution to etiopathogenesis and heterogeneity of ADHD should be investigated further.

A Case of the Perinatal Form Hypophosphatasia Caused by a Novel Large Duplication of the ALPL Gene and Report of One Year Follow-up with Enzyme Replacement Therapy

Hypophosphatasia (HPP) is a rare disease caused by mutations in the ALPL gene encoding tissue-non-specific isoenzyme of alkaline phosphatase (TNSALP). Duplications of the ALPL gene account for fewer than 1% of the mutations causing HPP. It has been shown that asfotase alfa enzyme replacement treatment (ERT) mineralizes the skeleton and improves respiratory function and survival in severe forms of HPP. Our patient was a newborn infant evaluated for respiratory failure and generalized hypotonia after birth. Diagnosis of HPP was based on low-serum ALP activity, high concentrations of substrates of the TNSALP and radiologic findings. On day 21 after birth, ERT using asfotase alfa (2 mg/kg three times per week, subcutaneous injection) was started. His respiratory support was gradually reduced and skeletal mineralization improved during treatment. We were able to discharge the patient when he was seven months old. No mutation was detected in the ALPL gene by all exon sequencing, and additional analysis was done by quantitative polymerase chain reaction (qPCR). As a result, a novel homozygote duplication encompassing exons 2 to 6 was detected. Early diagnosis and rapid intervention with ERT is life-saving in the severe form of HPP. qPCR can detect duplications if a mutation cannot be detected by sequence analysis in these patients.

Association of synaptosomal-associated protein 25 (SNAP-25) gene polymorphism with temperament and character traits in women with fibromyalgia syndrome

Abstract Background: Synaptosomal-associated protein 25 (SNAP-25) may be contribute to the pathogenesis of fibromyalgia Syndrome (FMS) by affecting the release of neurotransmitters. Objectives: We aimed to investigate the relationship between the SNAP-25 gen (DdeI = rs1051312 and MnlI = rs3746544) polymorphism and the temperament and character traits. Methods: A total of 85 female patients diagnosed with FMS and 70 age-matched healthy female subjects were enrolled into the study. The Temperament and Character Inventory (TCI) were performed on all the patients. SNAP-25 gene polymorphism was determined in the patients group and controls group. Results: No significant difference between groups was found regarding the distribution of SNAP-25 MnlI polymorphism (p > 0.05), but it was seen that the frequency of TC genotype for DdeI gene was higher in the patients group (p < 0.05). Increased hazard avoidance was found in the patients group (p < 0.05). When TCI scores were assessed in terms of SNAP-25 gene polymorphism, no statistically significant relationship was detected between the TT, TG, GG genotypes for MnlI gen and TCI scores (p > 0.05). However, increased hazard avoidance was detected in patients with TC genotype for DdeI gene compared to patients without such genotype. Discussion: SNAP-25 might be an etiological factor in FMS pathogenesis and might affect personality traits of FMS patients by mediating neurotransmitter release.

A variant allele of the Mediterranean-fever gene increases the severity of gout.

BACKGROUND: Gout is a clinical syndrome that occurs as an inflammatory response to increased concentration of uric acid and monosodium urate crystals. Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease with autosomal recessive inheritance. The Mediterranean fever (MEFV) gene is responsible for FMF and encodes pyrin that suppresses the inflammatory response. Most of the FMF-related mutations have been identified in exon 2 (e.g., E148Q and R202Q) and exon 10 (M680I, M694V, M694I and V726A) of the MEFV gene, and each missense mutation is known to increase production of interleukin-1, a proinflammatory cytokine. Our aim was to investigate effects of MEFV variant alleles on the manifestations of gout. METHODS: Seventy-one patients diagnosed with gout (age: 61.73 ± 11.73 years, F/M: 14/57) and 50 healthy subjects (age: 61.48 ± 11.97, F/M: 10/40) as controls were included in this study. RESULTS: MEFV variant alleles were found in 24 (33.8%) of the gout patients and in 13 (26%) of the control subjects; the difference was not statistically significant. In the gout patients with a MEFV variant allele, the interval between the first two attacks was shorter (P = 0.014), and the platelet count was higher (P = 0.026), compared to the patients without a variant allele. In addition, the patients with a MEFV variant allele showed the higher incidence of tophus (8.5% vs. 1.4%) (P = 0.005) and the higher number of attacks per year (P = 0.001). CONCLUSION: We propose that a variant allele of the MEFV gene may be responsible for the severity of gout.

Neonatal Bartter syndrome with cholelithiasis and hydrocephalus: Rare association.

Neonatal Bartter syndrome (NBS) is a rare autosomal recessive renal tubular disorder. This disease is characterized by hypokalemia, hypochloremia, and metabolic alkalosis that is often associated with failure to thrive and recurrent episodes of dehydration. The combination of BS and cholelithiasis in an infant is very rare. Herein, we report a premature male infant with NBS who developed cholelithiasis and hydrocephalus on clinical follow up. We recommend that periodic routine hepatobiliary ultrasonograpic screening for cholelithiasis should be performed in patients with NBS.

Quantitative comparison of immunohistochemical and PCR analysis of midkine expression in breast cancer types and serum midkine level.

BACKGROUND/AIM: Midkine (MK), a heparin-binding growth factor, has an important role in cancer progression. The aim of this study was to determine MK expression in breast tissue and the preoperative and postoperative serum levels of patients with breast cancer. MATERIALS AND METHODS: Sixty-one patients with breast cancer participated in our study. The MK serum levels were measured pre- and postoperatively for these patients. We also analyzed breast tissues of the 61 patients immunohistochemically. We examined serum midkine levels in 49 healthy volunteers. RESULTS: MK expression was observed in 44 (72.1%) of 61 breast cancer patients. In breast cancer patients the serum MK levels (3.68 ± 2.13 ng/mL (mean ± SD)) were significantly higher than in the control group (1.77 ± 0.38 ng/mL) before tumor removal (P = 0.000). After tumor removal, serum MK levels (2.47 ± 1.00 ng/mL) were significantly (P = 0.000) decreased according to preoperative levels. Increased serum levels of MK were related with tumor stages when clinical parameters were analyzed. CONCLUSION: We found that increased serum MK levels and protein expressions were associated with the carcinogenesis of breast cancer. MK levels decreased after tumor removal. According to our findings, MK might be a useful tumor marker for patients with breast cancer.

Familial mutation in Caffey disease with reduced penetrance: A case report.

Caffey disease is a rare condition of early infancy, characterized by soft tissue swelling, bone lesions, and hyperirritability. Its typical radiological finding is periosteal new bone formation. It can be sporadic or inherited in an autosomal dominant manner. There is no specific treatment. In symptomatic cases, non-steroidal anti-inflammatory drugs such as ibuprofen, indomethacin, or naproxen can be used. This is a report of an infant who presented with restlessness, irritability, and swelling over his shins, diagnosed as Caffey disease. Although there was no family history, the genetic analysis revealed heterozygous missense mutation (c.3040C > T) in type-I-collagen-alpha-1-chain gene in the patient in addition to his mother, grandmother, aunt, and cousin. After indomethacin therapy, the complaints of the patient were completely resolved and his bone lesions were significantly improved. This case report is a familial form of Caffey disease from Turkey, with proven heterozygous mutation in the patient and the family members.

MYD88 expression and L265P mutation in mature B-cell non-Hodgkin lymphomas.

BACKGROUND: Myeloid differentiation primary response 88 (MYD88) is a common adaptor protein that is responsible for signaling from several receptors; mutations in this gene may play a role in the pathogenesis of lymphoma. AIM: We aimed to determine the MYD88 L265P mutation frequency, the level of MYD88 expression, and their associations with clinicopathological parameters in mature B-cell non-Hodgkin lymphomas (NHLs). METHODS: A total of 68 patients were included in the study. The presence of the MYD88 L265P mutation was analyzed by real-time polymerase chain reaction and direct sequencing. MYD88 protein expression was evaluated by immunohistochemistry (IHC) using two different scoring systems. RESULTS: MYD88 L265P mutation was present in eight (18.6%) diffuse large B-cell lymphoma (DLBCL) patients. We also observed a significant association between the loss of MYD88 expression and advanced stage in both mature B-cell NHL and DLBCL according to the first IHC scoring systems (p=0.015 and p=0.024, respectively). An association was also seen between MYD88 overexpression and low clinical risk in both mature B-cell NHL and DLBCL according to the second IHC scoring system (p=0.027 and p=0.024, respectively). CONCLUSIONS: The L265P mutation may be helpful for understanding the pathogenesis of immune-privileged site-associated DLBCLs. The presence of the mutation, together with its protein overexpression, could also be used as a prognostic marker in advanced stage DLBCLs.

Possible Role of GADD45γ Methylation in Diffuse Large B-Cell Lymphoma: Does It Affect the Progression and Tissue Involvement?

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma among adults and is characterized by heterogeneous clinical, immunophenotypic, and genetic features. Different mechanisms deregulating cell cycle and apoptosis play a role in the pathogenesis of DLBCL. Growth arrest DNA damage-inducible 45 (GADD45γ) is an important gene family involved in these mechanisms. The aims of this study are to determine the frequency of GADD45γ methylation, to evaluate the correlation between GADD45γ methylation and protein expression, and to investigate the relation between methylation status and clinicopathologic parameters in DLBCL tissues and reactive lymphoid node tissues from patients with reactive lymphoid hyperplasia. MATERIALS AND METHODS: Thirty-six tissue samples of DLBCL and 40 nonmalignant reactive lymphoid node tissues were analyzed in this study. Methylation-sensitive high-resolution melting analysis was used for the determination of GADD45γ methylation status. The GADD45γ protein expression was determined by immunohistochemistry. RESULTS: GADD45γ methylation was frequent (50.0%) in DLBCL. It was also significantly higher in advanced-stage tumors compared with early-stage (p=0.041). In contrast, unmethylated GADD45γ was associated with nodal involvement as the primary anatomical site (p=0.040). CONCLUSION: The results of this study show that, in contrast to solid tumors, the frequency of GADD45γ methylation is higher and this epigenetic alteration of GADD45γ may be associated with progression in DLBCL. In addition, nodal involvement is more likely to be present in patients with unmethylated GADD45γ.

Could serum pentraxin 3 levels and IgM deposition in skin biopsies predict subsequent renal involvement in children with Henoch-Schönlein purpura?

BACKGROUND: The aim of this study was to evaluate the potential of serum pentraxin 3 (PTX3) values as an early predictor of subsequent renal involvement in patients with Henoch-Schönlein purpura (HSP) with no abnormalities on urinary examination and in renal function tests at disease onset. METHODS: This was a prospective cohort study which included 60 pediatric patients with HSP (age range 3-15 years) who were diagnosed between February 2011 and October 2012 and 60 age- and sex-matched healthy controls. The patients were followed up for at least 18 months. Clinical findings were recorded for all patients at first examination, and blood samples for routine laboratory parameters and PTX3 value as well as skin biopsy specimens were obtained from each subject. RESULTS: Of the 60 patients with HSP, 29 (48.3 %) developed subsequent renal involvement, of whom four underwent kidney biopsy. The mean serum PTX3 level of patients with subsequent renal involvement was significantly higher than those of patients without renal involvement and of the controls (2.20 ± 1.30 vs. 1.36 ± 0.85 and 1.03 ± 0.7 ng/ml, respectively; p = 0.004). Immunofluorescence evaluation of skin biopsy revealed that in addition to immunoglobulin A (IgA) deposition, the IgM deposition was significantly associated with subsequent renal involvement (p = 0.008). CONCLUSIONS: A high PTX3 level and IgM staining in skin biopsies from HSP patients may be harbingers of subsequent renal involvement.

HIF1A as a major vascular endothelial growth factor regulator: do its polymorphisms have an association with age-related macular degeneration?

BACKGROUND: To investigate the association between age-related macular degeneration (AMD) and the polymorphisms of HIF1A, a major vascular epithelial growth factor regulator under hypoxic conditions. The associations of AMD and polymorphisms of genes CFH, SKIV2L and MYRIP were also studied. DESIGN: Prospective study. PARTICIPANTS: Eighty-seven AMD patients and 80 healthy subjects admitted to the Department of Ophthalmology at Pamukkale University Hospital, Denizli, Turkey, were included: 45 (52%) had wet type AMD, and 42 (48%) had dry type AMD. METHODS: Polymorphisms rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and both rs11549465 and rs11549467 (HIF1A) were investigated in DNA isolated from peripheral blood samples of the cases and controls by dye-termination DNA sequencing. MAIN OUTCOME MEASURES: Genotype distribution of rs1061170 (CFH), rs429608 (SKIV2L), rs2679798 (MYRIP) and both rs11549465 and rs11549467 (HIF1A) in AMD cases and healthy controls; association between genotypes and AMD subtypes. RESULTS: Given the significant difference between the mean age of case and control groups (72.13 ± 5.77 vs. 62.80 ± 5.22, respectively) (P = .000), subsequent analyses were adjusted for age. We found that having at least one C allele for polymorphism rs1061170 increases AMD risk independent of age (OR = 2.42, 95% confidence interval [CI], 1.22-4.81). The ancestral T allele for polymorphism rs1061170 has a protective effect for AMD (OR = 0.53, 95% CI, 0.34-0.83). No statistically significant difference for distributions of other single nucleotide polymorphisms (SNPs) emerged between patients and healthy subjects. CONCLUSIONS: No associations appeared between HIF1A SNPs and AMD, which were studied here for the first time; however, polymorphism rs1061170 of the CFH gene is associated with AMD in our population.

Synaptosomal-associated protein 25 (Snap-25) gene polymorphism frequency in fibromyalgia syndrome and relationship with clinical symptoms.

BACKGROUND: SNAP-25 protein is contributory to plasma membrane and synaptic vesicle fusions that are critical points in neurotransmission. SNAP-25 gene is associated with behavioral symptoms, personality and psychological disorders. In addition, SNAP-25 protein can be related to different neurotransmitter functions due to its association with vesicle membrane transition and fusion. This is important because neurologic, cognitive, and psychologic disorders in fibromyalgia syndrome (FMS) can be related to this function. This relationship may be enlightening for etiopathogenesis of FMS and treatment approaches. We aimed to study a SNAP-25 gene polymorphism, which is related to many psychiatric diseases, and FMS association in this prospective study. METHODS: We included 71 patients who were diagnosed according to new criteria and 57 matched healthy women in this study. Both groups were evaluated regarding age, height, weight, BMI, education level, marital and occupational status. A new diagnosis of FMS was made from criteria scoring, SF-36, Beck depression scale, and VAS that were applied to the patient group. SNAP-25 gene polymorphism and disease activity score correlations were compared. RESULTS: Mean age was 38±5,196 and 38.12±4.939 in patient and control groups, respectively (p=0.542). No significant difference was found between groups regarding age, height, weight, BMI, education level, marital or occupational status (p > 0.05). Ddel T/C genotype was significantly higher in the patient group (p = 0.009). MnlI gene polymorphism did not show a correlation with any score whereas a significant correlation was found between Ddel T/C genotype and Beck depression scale and VAS score (p < 0.05). CONCLUSION: FMS etiopathogenesis is not clearly known. Numerous neurologic, cognitive and psychological disorders were found during studies looking at cause. Our study showed increased SNAP-25 Ddel T/C genotype in FMS patients compared to the control group, which is related to behavioral symptoms, personality and psychological disorders in FMS patients.

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.

The determination of relationship between "excision repair cross-complementing group 1" (ERCC1) gene T19007C and C8092A single nucleotide polymorphisms and clinicopathological parameters in non-small cell lung cancer.

DNA repair plays a key role in prevention of carcinogenesis and one of the most important DNA repair mechanisms is nucleotide excision repair (NER) pathway. This pathway includes a number of genes such as excision repair cross-complementing group 1 (ERCC1) gene which are responsible for the 5' incision of damaged DNA. A reduced DNA repair capacity associated with ERCC1 mRNA level has been observed in lung carcinogenesis. Two single nucleotide polymorphisms (SNPs) in ERCC1 gene, T19007C (rs11615) and C8092A (rs3212986), reportedly predict to affect the mRNA of ERCC1 in non-small cell lung cancer (NSCLC). To examine the role of two common SNPs in ERCC1 gene further, we conducted this study where 80 cases histopatologically diagnosed as NSCLC were genotyped. Genomic DNA was extracted from formalin-fixed, paraffin embedded tissues and two SNPs were analyzed using real-time PCR. The distributions of TT, TC, and CC genotypes of the T19007C SNP were 40, 44 and 16%, respectively. Significantly increased frequency of the patients carrying at least one 19007C allele was observed in early stage compared to advanced stage (P=0.002). And also, the frequency of TC and CC genotypes significantly increased in younger patients compared to older patients (P=0.035). Regarding C8092A SNP, the distribution of CC, CA, and AA genotypes was 38, 51 and 11%, respectively. There was no significant difference in the genotype distribution between C8092A SNP and clinicopathological parameters. This study indicated that harboring at least one 19007C allele may have protective effect in NSCLC.

Expression of ERCC1 and its clinicopathological correlations in non-small cell lung cancer.

Excision Repair Cross-Complementing Group 1 (ERCC1) is an important DNA repair gene, playing critical role in nucleotide excision repair pathway and having a significant influence on genomic instability. Some studies support that ERCC1 might be a potential predictive and prognostic marker in non-small cell lung cancer (NSCLC). ERCC1 has also been shown to be a promising biomarker in NSCLC treated with a cisplatin-based regimen. Therefore, the determination of ERCC1 expression at DNA, mRNA and protein level in different stages of NSCLC is still an important topic in the cancer. Ninety-one formalin-fixed paraffin-embedded tumor samples histopathologically diagnosed as NSCLC were examined in this study. ERCC1 expression at protein level were scored by immunohistochemistry. The gene amplification and mRNA expression levels for ERCC1 were determined by real-time quantitative PCR. There was complete concordance among the three methods in 39 tumor samples (42.9%). A strong correlation was found between DNA amplification and mRNA expression (r=0.662) while there was no correlation between mRNA and protein assessment for ERCC1 expression (r=-0.013). ERCC1 expression at mRNA and DNA level (63.1 and 84.2%, respectively) in tumors at stage III was higher than at the other stages. In contrast, the protein expression at stage II and III (56.6 and 52.6%, respectively) of NSCLC was lower than that of tumors with stage I NSCLC. These results show that the mechanism by which ERCC1 expression might play a role in tumor behavior. This study was also confirmed that the appropriate validation and qualification in methods used for ERCC1 status were needed before its clinical application and implementation.