The association between methylation levels of targeted genes and albuminuria in patients with early diabetic kidney disease.

OBJECTIVE: The incidence of diabetes and its complications are greatly increasing world-wide. Diabeticnephropathy (DN) is the main cause of end-stage renal disease and is associated with high morbidity and mortality. It is important to predict patients with high risk for DN in the early stage. We selected the genes which have an important role on diabetic kidney disease. We aimed to investigate the association between DNA methylation levels of targeted genes and albuminuria in patients with early DN. METHODS: We collected the clinical data of patients with type 2 diabetes mellitus. We measured spot urine albumin creatinine ratio to calculate albuminuria level. We divided patients into two groups based on albumin excretion as patients with (n = 69) and without DN (n = 27). We performed methylation profiling after bisulfite conversion by pyrosequencing method. The mean value of percent methylation level of each gene was calculated. RESULTS: We compared targeted genes (TIMP-2, AKR1B1, MMP-2, MMP-9, MYL9, SCL2A4, SCL2A1, SCL4A3) methylation levels and albuminuria. We found significant negative correlation between TIMP-2 and AKR1B1 gene methylation levels and albuminuria levels. CONCLUSIONS: The present study provided evidence that hypomethylation of TIMP-2 and AKR1B1 genes can be associated with albuminuria in patients with early DN. We may speculate that the hypomethylation of TIMP-2 and AKR1B1 genes may be an early surrogate marker of DN.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in psoriasis in southern Turkey.

BACKGROUND:: Psoriasis is a multigenic and multifactorial dermatological disease linked to cardiovascular diseases. Increased levels of homocysteine in patients with psoriasis have been demonstrated in many studies. The most frequently investigated genetic defect that plays a role in homocysteine metabolism is single point substitution (C to T) located on the 677th nucleotide of the methylenetetrahydrofolate reductase gene (MTHFR). OBJECTIVE:: In this study, we aimed to investigate methylenetetrahydrofolate C677T polymorphism in psoriasis patients in Turkey. METHODS:: The study included 96 patients with psoriasis and 77 controls from southern Turkey. Methylenetetrahydrofolate C677T polymorphism was analysed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism methods. RESULTS:: In the psoriasis group, 34 CC (35.4%), 46 CT (47.9%) and 16 TT (16.7%) genotypes were found, respectively; while in the control group, the figures were 39 (50.6%), 35 (45.5%), 3 (3.9%). Homozygote and heterozygote T alleles of methylenetetrahydrofolate C677T polymorphism were significantly higher in the psoriasis than in the control group (p=0.013). CONCLUSION:: We firstly found a correlation between methylenetetrahydrofolate C677T polymorphism and psoriasis among the southern Turkish population.

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in psoriasis in southern Turkey

Abstract: Background: Psoriasis is a multigenic and multifactorial dermatological disease linked to cardiovascular diseases. Increased levels of homocysteine in patients with psoriasis have been demonstrated in many studies. The most frequently investigated genetic defect that plays a role in homocysteine metabolism is single point substitution (C to T) located on the 677th nucleotide of the methylenetetrahydrofolate reductase gene (MTHFR). Objective: In this study, we aimed to investigate methylenetetrahydrofolate C677T polymorphism in psoriasis patients in Turkey. Methods: The study included 96 patients with psoriasis and 77 controls from southern Turkey. Methylenetetrahydrofolate C677T polymorphism was analysed using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism methods. Results: In the psoriasis group, 34 CC (35.4%), 46 CT (47.9%) and 16 TT (16.7%) genotypes were found, respectively; while in the control group, the figures were 39 (50.6%), 35 (45.5%), 3 (3.9%). Homozygote and heterozygote T alleles of methylenetetrahydrofolate C677T polymorphism were significantly higher in the psoriasis than in the control group (p=0.013). Conclusion: We firstly found a correlation between methylenetetrahydrofolate C677T polymorphism and psoriasis among the southern Turkish population.

Malouf syndrome with hypergonadotropic hypogonadism and cardiomyopathy: two-case report and literature review.

Malouf syndrome is a very rarely encountered syndrome which was first diagnosed in 1985 upon the examination of two sisters, with findings of hypergonadotropic hypogonadism, dilated cardiomyopathy, blepharoptosis, and broad nasal base. Later on, Narahara diagnosed another sporadic case with the same findings. A survey of relevant literature leads us to three women cases in total. Here we present two cases of Malouf syndrome and literature review.

Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools.

Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.

The spectrum of ß-thalassemia mutations in Hatay, Turkey: reporting three new mutations.

ß-Thalassemia (ß-thal) is an important health problem in Hatay, Southern Turkey, because of its high carrier frequency and the frequency of consanguinity. The aim of this study was to reveal the spectrum of ß-thal mutations and to provide a foundation for prenatal genetic testing that will be a part of an effective prevention program for ß-thal disease in Hatay. We determined the spectrum of ß-thal mutations in 93 unrelated affected patients. Using a direct sequencing method, we identified a large number of ß-thal mutations. We found different results from other parts of Turkey. A total of 16 different ß-thal mutations were characterized in the parents. The most common mutations were: IVS-I-110 (G>A), IVS-I-6 (T>C), IVS-I-1 (G>A), frameshift codon (FSC) 8 (-AA), codon 39 (C>T) and IVS-II-745 (C>G). Since our region has seen many Syrian and Iraqi immigrants, we report that the prevalence of the thalassemia traits are different from other regions of Turkey. Our study demonstrates the spectrum of ß-thal mutations in the Hatay region, and that there was great molecular heterogeneity.

Urotensin II (U-II), a novel cyclic peptide, possibly associated with the pathophysiology of osteoarthritis.

Synovial fibrosis is one of the main outcomes of osteoarthritis. Some authors have reported that urotensin-II (U-II) may cause pathologic fibrosis in cardiovascular system, lung and liver. However there are no previous reports available in the literature about its relationship with the synovial fibrosis in osteoarthritis. The aim of this study was to compare the U-II levels in knee synovial fluids obtained from osteoarthritic and non-osteoarthritic patients. Two groups were created, the osteoarthritis group and non-osteoarthritic control group. The control group was consisted of patients who underwent arthroscopic surgery for other reasons than cartilage disorders. In the osteoarthritis group all patients had grade 4 primer degenerative osteoarthritis and were treated with total knee arthroplasty. Minimum 1 mL knee synovial fluids were obtained during operation. Levels of U-II were measured by using ELISA kit U-II levels were significantly higher in the osteoarthritic group than that in the control group. No correlation was found between U-II levels and age. In conclusion, the significantly high U-II levels in the knee synovial fluid of osteoarthritic patients supported our hypothesis that "U-II may be associated with the synovial fibrosis in osteoarthritis".

Are low maternal estriol levels a predictor for pro-opiomelanocortin (POMC) deficiency caused by POMC mutation during pregnancy?

Isolated adrenocorticotropic hormone deficiency is a rare cause of adrenocortical insufficiency, especially in children, and may be an underestimated cause of neonatal death. Low estriol levels are usually correlated with compromised uteroplacental perfusion and associated with fetal death. A 30-years old woman applied for pregnancy follow-up. Ultrasonographic evaluation and karyotype of the fetus are normal. Low estriol level 0.34 MoM (% 0.24) was detected in maternal triple screening test. Amniocentesis was performed, and chromosomal disorders, steroid sulfatase deficiency, and Smith-Lemli-Opitz syndrome (SLOS) were excluded with karyotype, fluorescence in situ hybridization (FISH), and molecular analysis of SLOS, respectively. As their first child had pro-opiomelanocortin (POMC) deficiency, POMC gene analysis was performed from both amniotic fluid and ethylene diamine tetra aceticacid (EDTA) blood sample of affected previous child, and homozygote mutation was detected. Fetus is diagnosed as POMC deficiency. We are presenting this case to discuss possible relationship of low maternal E3 levels and fetal POMC deficiency.

Three patients resembling Teebi-Shaltout syndrome.

Teebi-Shaltout syndrome (TSS) was first reported by Teebi and Shaltout in 1989. This entity is proposed to be inherited in autosomal recessive manner. The clinical features include characteristic facial features, ectodermal dysplasia, camptodactyly, and caudal appendage. Only one additional paper reporting four additional cases has been published since the first description. Clinical features common to all previously affected individuals diagnosed with TSS are craniofacial, orodental-ectodermal, and skeletal. This report summarizes and discusses the findings of three additional patients from two unrelated families with findings similar to TSS. These findings may be present in a genetically and phenotypically heterogeneous group of disorders similar to TSS. Presence of consanguinity and similarly affected siblings of both genders suggests autosomal recessive inheritance.

Wiedemann-Rautenstrauch syndrome: report of a variant case.

Wiedemann-Rautenstrauch syndrome (WRS) is a rare autosomal recessive disorder that includes premature aging phenotype at birth. The condition is also known as a neonatal progeroid syndrome. Up to now only a few published case reports have been documented. The syndrome is characterized by progeroid appearance, decreased subcutaneous fat, hypotrichosis, macrocephaly, and in some natal teeth. We describe a new patient with features of bilaterally pelvicalyceal ectasia and partial syndactyly on 2th and 3th toes, not previously described, to our knowledge.