MEFV mutation frequencies in a Turkish cohort with low prevalence of familial Mediterranean fever

Background/aim: Familial Mediterranean fever (FMF) is a genetically recessive autoinflammatory disease caused by mutations in the Mediterranean fever (MEFV) gene. The aim of this study was to investigate the frequencies of the most common MEFV mutations among a sample of healthy individuals from the Havsa population of European Turkey, where FMF is less prevalent compared to Asian Turkey. Materials and methods: The study group consisted of 263 unrelated healthy adults. All of the participants were analyzed for the M694V, V726A, M680I, and E148Q mutations in the MEFV gene. Results: In total, 25 of the 263 individuals carried MEFV mutations (9.5%). The observed allele frequencies were 1.5% for M694V (95% confidence interval [CI] 0.5-2.5), 2.6% for E148Q (95% CI 1.6-3.9), 0.5% for M680I (95% CI 0.0-1.1), and 0.0% for V726A. The frequencies of the M694V, M680I, and E148Q mutations were not significantly different from allele frequencies (approximately 20%) determined for other regions of Turkey where FMF is more prevalent. Conclusion: These data suggest that the positivity of the MEFV gene mutation tests have lower predictive value in a population with low FMF prevalence.

Mutations in Core Gene Region of Hepatitis B Virus in Patients with Chronic Hepatitis B.

BACKGROUND: The HBV core protein plays a major role in host immune response. Mutations occurring in the HBV core gene may cause alterations in the major epitopes being effective in the host immune response. Until now, the persistent effects of core gene mutations on HBV infections have not been fully understood. The aim of this study is to analyze the core gene mutations for epitopes in the T lymphocytes [T helper (Th) and cytotoxic (CTL)] and B cell and C terminal region in patients with chronic hepatitis using ultra-deep pyrosequencing (UDPS) method. METHODS: Eleven patients with chronic hepatitis B infection were included in the study. Amplification of the core gene was performed by a conventional PCR method. Mutations in the epitopes for T lymphocytes (Th and CTL) and B cell and in the C terminal region of HBV core gene were screened by UDPS. These mutations were analyzed in HBeAg positive and negative patients. RESULTS: The minimum percentages of amino acid substitutions were found with 0.9% in HBeAg positive patients and 1.2% in negative patients. The number of missense mutation was higher in patients with HBeAg positive than negative patients (p < 0.005). The number of amino acid substitutions in the region of aa49 - 69 in the Th epitopes was found to be the highest in both HBeAg positive and negative patients. The mutation frequency was higher in the C-terminal region of the core protein compared to the Th, CTL, and B cell regions and these were more common in subjects with high-grade fibrosis. Some types of mutations (V27I, R47H, Y132I, R174STOP, S181P, Q182K) were only detected in subjects with liver cirrhosis. CONCLUSIONS: Unlike literature, our results show that there is no significant increase in number of mutations in the core gene of the virus during the anti-HBe positive period. The role of low abundance variants and mutations in the immune system can be understood using methods such as UDPS in the near future.

Analysis of Hepatitis C Virus NS5A Region in Patients with Cirrhosis Using an Ultra-Deep Pyrosequencing Method.

BACKGROUND: HCV (Hepatitis C Virus) is genetically more diverse than HBV and HIV (Human Immunodeficiency Virus) and exists as quasispecies within infected individuals. This is due to the lack of efficient proofreading of the viral RNA-dependent RNA polymerase. Consequently, quasispecies emerge depending on the mutation rate of the viral polymerase, which may display a high level of genetic variability in a population. In infected individuals, HCV replicates and circulates as quasispecies composed of a complex mixture of different but closely related genomes that undergoes continuous change due to competitive selection and cooperation between arising mutants. The aim of this study is to investigate mutations in the NS5A region as a whole, including ISDR, PKRBD, IRRDR, and V3 of HCV genotype 1b cirrhosis patients being naive and nonresponders, treated with IFN (interferon) + ribavirin (RBN) by using an ultra-deep pyrosequencing method (UDPS). METHODS: During the study, five patients (four females, and one male, mean age 59.8 ± 11 years) with HCV related cirrhosis were analyzed. Three patients received IFN + RBN for six months, but two patients did not receive any therapy. HCV-RNA concentrations in patients' sera were determined using a COBAS AMPLICOR HCV MONITOR Test, Version 2.0. Genotyping was performed by using a commercial reverse hybridization method, Line Probe Assay. The quasispecies for the NS5A region were investigated using UDPS. RESULTS: All five patients were HCV genotype 1b (Mean Child-Pugh score 7.2 ± 1.9, 2 pts Child A, 2 pts Child B, and one pt Child C) but only one patient had hepatocellular carcinoma (HCC). A total of 19 different mutations were detected in each of the five patients (ranging from 3 to 6 mutations per patient). In all five patients, several mutations in the ISDR and PKR-BD regions were detected. On the other hand, mutations in the V3 and IRRDR regions were only detected in one patient. CONCLUSIONS: UDPS is a new sequencing technology and a very sensitive method in detection of quasispecies with low frequency NS5A region mutations. These mutations may affect the antiviral response and development of HCC. However, further studies in larger number of patients should be conducted to clarify this hypothesis.

Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease.

Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 × 10(-5)), and one gene involved in innate immunity, TLR4 (P = 8.0 × 10(-4)), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063-0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 × 10(-12)). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis.

Water as Source of Francisella tularensis Infection in Humans, Turkey.

Francisella tularensis DNA extractions and isolates from the environment and humans were genetically characterized to elucidate environmental sources that cause human tularemia in Turkey. Extensive genetic diversity consistent with genotypes from human outbreaks was identified in environmental samples and confirmed water as a source of human tularemia in Turkey.

Mitochondrial mutations in patients with congenital heart defects by next generation sequencing technology.

It has been shown that mitochondrial deoxyribo nucleic acid mutations may play an important role in the development of cardiomyopathy, and various types of cardiomyopathy can be attributed to disturbed mitochondrial oxidative energy metabolism. Several studies have described many mutations in mitochondrial genes encoding for subunits of respiratory chain complexes. Thus, recent studies confirm that pathologic mitochondrial deoxyribo nucleic acid mutations are a major reason of diseases and determining them by next-generation sequencing will improve our understanding of dysregulation of heart development. To analyse mitochondrial deoxyribo nucleic acid mutations, the entire mitochondrial deoxyribo nucleic acid was amplified in two overlapping polymerase chain reaction fragments from the cardiac tissue of the 22 patients with congenital heart disease, undergoing cardiac surgery. Mitochondrial deoxyribo nucleic acid was deep sequenced by next-generation sequencing. A total of 13 novel mitochondrial deoxyribo nucleic acid mutations were identified in nine patients. Of the patients, three have novel mutations together with reported cardiomyopathy mutations. In all, 65 mutations were found, and 13 of them were unreported. This study represents the most comprehensive mitochondrial deoxyribo nucleic acid mutational analysis in patients with congenital heart disease.

Metagenomic analysis of the microbial community in kefir grains.

Kefir grains as a probiotic have been subject to microbial community identification using culture-dependent and independent methods that target specific strains in the community, or that are based on limited 16S rRNA analysis. We performed whole genome shotgun pyrosequencing using two Turkish Kefir grains. Sequencing generated 3,682,455 high quality reads for a total of ∼1.6 Gbp of data assembled into 6151 contigs with a total length of ∼24 Mbp. Species identification mapped 88.16% and 93.81% of the reads rendering 4 Mpb of assembly that did not show any homology to known bacterial sequences. Identified communities in the two grains showed high concordance where Lactobacillus was the most abundant genus with a mapped abundance of 99.42% and 99.79%. This genus was dominantly represented by three species Lactobacillus kefiranofaciens, Lactobacillus buchneri and Lactobacillus helveticus with a total mapped abundance of 97.63% and 98.74%. We compared and verified our findings with 16S pyrosequencing and model based 16S data analysis. Our results suggest that microbial community profiling using whole genome shotgun data is feasible, can identify novel species data, and has the potential to generate a more accurate and detailed assessment of the underlying bacterial community, especially for low abundance species.

A novel ATP8 gene mutation in an infant with tetralogy of Fallot.

We report the case of a novel mitochondrial DNA mutation in the MT-ATP8 gene in an infant with tetralogy of Fallot. Next-generation sequencing was applied to sequence whole mitochondrial DNA of the patient. A known Leber's hereditary optic neuropathy-associated mutation (G9804A), a heteroplasmic T7501C mutation (17%), and a novel C8481 T Pro > Leu missense mutation in the MT-ATP8 gene was identified.

The effect of vascular endothelial growth factor overexpression in experimental necrotizing enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC) is a serious condition, predominantly observed in premature infants. We used an experimental NEC model to investigate the effects of vascular endothelial growth factor (VEGF) cloned into a plasmid. MATERIALS AND METHODS: Twenty-four newborn Wistar albino rats were randomized equally into three groups as follows: control, NEC and NEC+VEGF. NEC was induced by hyperosmolar enteral formula feeding, exposure to hypoxia/reoxygenation and cold stress. In the NEC+VEGF group, VEGF (1 µg) incorporated into plasmid (2 µg) was administered subcutaneously once daily for a total of 3 days starting on the first day of the NEC procedure. All rats were sacrificed on the 4th day of life, and the specimens were harvested for histopathological and biochemical examinations [including tissue oxidative stress (malondialdehyde and nitric oxide), inflammation (myeloperoxidase, interleukin-6 and tumor necrosis factor alpha) and apoptosis (caspase-3 activity) parameters]. RESULTS: In the NEC+VEGF group, tissue malondialdehyde, nitric oxide, interleukin-6, tumor necrosis factor alpha levels and caspase-3 activity were significantly decreased. In addition, the myeloperoxidase level was increased compared to that of the NEC group (p < 0.05). Histopathologically, VEGF overexpression enhanced angiogenesis, alleviated villous atrophy and tissue edema (p < 0.05). CONCLUSION: VEGF overexpression with plasmids seems to be a promising approach in the management of NEC.

MEFV gene variations in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to investigate the frequency of familial Mediterranean fever (FMF)-associated MEFV gene variations in patients with systemic lupus erythematosus (SLE). METHODS: The study group comprised 190 SLE patients and 101 healthy controls of Turkish origin with no clinical features of FMF. All individuals were genotyped for the four most common MEFV gene variations (M694V, M680I, V726A and E148Q) by PCR-restriction fragment length polymorphism analysis. RESULTS: The frequency of carrying any of the four MEFV gene variations under study was 15 % in patients with SLE and 10 % in the healthy controls (p = 0.23). After the exclusion of the less penetrant E148Q variation, re-analysis for the three penetrant mutations revealed a significant association between exon 10 variations and pericarditis [p = 0.038, odds ratio (OR) 3.5, 95 % confidence interval (CI) 1.0-12.1], and pleural effusion (p = 0.043, OR 5.2, 95 % CI 0.8-30.9). No significant association was detected between the MEFV gene variations and a higher acute phase response. CONCLUSIONS: The MEFV gene variations analyzed in our study do not seem to increase the overall susceptibility to SLE and do not have any strong association with its clinical manifestations. The possibility of a modest effect of penetrant exon 10 MEFV variants on the development of serosal effusions needs to be explored in a larger series of patients.

Association between endothelial nitric oxide synthase intron 4a/b polymorphism and aortic dissection.

OBJECTIVES: The genetic risk factors that contribute to the risk of developing aortic dissection (AD) have been studied. We assessed the association of endothelial nitric oxide synthase (eNOS) gene polymorphism with AD. STUDY DESIGN: Patients who underwent surgery with the diagnosis of AD and survived after the operation in our center between May 2007 and June 2011 were recruited retrospectively. The eNOS intron 4a/b polymorphism was determined by polymerase chain reaction (PCR) using oligonucleotide primers (sense: 5'-AGGCCCTATGGTAGTGCCTTT-3'; antisense: 5'-TCTCTTAGTGCTGTGGTCAC-3') that flank the region of the 27 bp VNTR in intron 4. RESULTS: Thirty-nine patients (88%) had type A AD, while the remainder (12%) had type B AD. The distribution of eNOS4 a/b gene polymorphism differed significantly from the control group, with higher frequencies of eNOS 4a/a and 4a/b genotypes in the AD group (x(2)=7.16, p=0.03). CONCLUSION: In this study, the distribution of eNOS genotypes differed between the AD and control groups; however, this polymorphism was not found to be an independent factor for the development of AD.

Alix protein is substrate of Ozz-E3 ligase and modulates actin remodeling in skeletal muscle.

Alix/AIP1 is a multifunctional adaptor protein that participates in basic cellular processes, including membrane trafficking and actin cytoskeleton assembly, by binding selectively to a variety of partner proteins. However, the mechanisms regulating Alix turnover, subcellular distribution, and function in muscle cells are unknown. We now report that Alix is expressed in skeletal muscle throughout myogenic differentiation. In myotubes, a specific pool of Alix colocalizes with Ozz, the substrate-binding component of the muscle-specific ubiquitin ligase complex Ozz-E3. We found that interaction of the two endogenous proteins in the differentiated muscle fibers changes Alix conformation and promotes its ubiquitination. This in turn regulates the levels of the protein in specific subcompartments, in particular the one containing the actin polymerization factor cortactin. In Ozz(-/-) myotubes, the levels of filamentous (F)-actin is perturbed, and Alix accumulates in large puncta positive for cortactin. In line with this observation, we show that the knockdown of Alix expression in C2C12 muscle cells affects the amount and distribution of F-actin, which consequently leads to changes in cell morphology, impaired formation of sarcolemmal protrusions, and defective cell motility. These findings suggest that the Ozz-E3 ligase regulates Alix at sites where the actin cytoskeleton undergoes remodeling.

Role of the line probe assay INNO-LiPA HBV DR and ultradeep pyrosequencing in detecting resistance mutations to nucleoside/nucleotide analogues in viral samples isolated from chronic hepatitis B patients.

Despite the effectiveness of nucleoside/nucleotide analogues in the treatment of chronic hepatitis B (CHB), their long-term administration is associated with the emergence of resistant hepatitis B virus (HBV) mutants. In this study, mutations resulting in antiviral resistance in HBV DNA samples isolated from 23 CHB patients (nine treatment naïve and 14 treated previously) were studied using a line probe assay (INNO-LiPA HBV DR; Innogenetics) and ultradeep pyrosequencing (UDPS) methods. Whilst the INNO-LiPA HBV DR showed no resistance mutations in HBV DNA samples from treatment-naive patients, mutations mediating lamivudine resistance were detected in three samples by UDPS. Among patients who were treated previously, 19 mutations were detected in eight samples using the INNO-LiPA HBV DR and 29 mutations were detected in 12 samples using UDPS. All mutations detected by the INNO-LiPA HBV DR were also detected by UDPS. There were no mutations that could be detected by INNO-LiPA HBV DR but not by UDPS. A total of ten mutations were detected by UDPS but not by INNO-LiPA HBV DR, and the mean frequency of these mutations was 14.7 %. It was concluded that, although INNO-LiPA HBV DR is a sensitive and practical method commonly used for the detection of resistance mutations in HBV infection, UDPS may significantly increase the detection rate of genotypic resistance in HBV at an early stage.

Application of canonical correlation analysis for identifying viral integration preferences.

MOTIVATION: Gene therapy aims at using viral vectors for attaching helpful genetic code to target genes. Therefore, it is of great importance to develop methods that can discover significant patterns around viral integration sites. Canonical correlation analysis is an unsupervised statistical tool that is used to describe the relations between two related views of the same semantic object, which fits well for identifying such salient patterns. RESULTS: Proposed method is demonstrated on a sequence dataset obtained from a study on HIV-1 preferred integration regions. The subsequences on the left and right sides of the integration points are given to the method as the two views, and statistically significant relations are found between sequence-driven features derived from these two views, which suggest that the viral preference must be the factor responsible for this correlation. We found that there are significant correlations at x=5 indicating a palindromic behavior surrounding the viral integration site, which complies with the previously reported results. AVAILABILITY: Developed software tool is available at http://ce.istanbul.edu.tr/bioinformatics/hiv1/.

Characterization of H3K9me3- and H4K20me3-associated circulating nucleosomal DNA by high-throughput sequencing in colorectal cancer.

Modified histone tails in nucleosomes circulating in the blood bear the potential as cancer biomarkers. Recently, using chromatin immunopecipitation (ChIP)-related quantitative PCR, we described reduced plasma levels of the two pericentric heterochromatin-specific histone methylation marks H3K9me3 and H4K20me3 in patients with colorectal cancer (CRC). Here, by utilizing ChIP-related high-throughput sequencing, we further characterized these modifications in circulation. Plasma DNA from nucleosomes immunoprecipitated by H3K9me3- and H4K20me3-specific antibodies from patients with CRC (N = 15) and healthy subjects (N = 15) was subjected to the Roche 454 FLX sequencing, and the generated array of ChIP-enriched sequences were compared to the human reference genome. The total number of nucleosomes, of sequence reads and of diverse DNA repetitive elements were statistically compared between the study groups. Total nucleosome amount was not different in both groups. Concerning both histone modifications, lower numbers of sequence reads were detected in CRC patients as compared with healthy controls (medians in H3K9me3: 32 vs. 61; p < 0.01; in H4K20me3: 54 vs. 88; p < 0.01). Size of fragments was not different in both groups. Most abundant sequences were repetitive LINE and SINE elements while simple repeats, LTR, DNA, SAT, and low complexity elements were less frequent. Best discrimination between both groups was achieved by total number of H3K9me3 reads (AUC 0.90) and H3K9me3 LINE elements L1 (AUC 0.93) und L2 (AUC 0.91). The present results confirm earlier findings of lower H3K9me3 levels in CRC and show LINE elements to be the most frequent and best discriminative markers on modified histones.

Effects of curcumin on proinflammatory cytokines and tissue injury in the early and late phases of experimental acute pancreatitis.

BACKGROUND & AIMS: Acute pancreatitis (AP) varies from mild to severe necrotizing changes with high mortality. The objective of the current study was to investigate the effects of curcumin on tissue injury and proinflammatory cytokines in the early and late phases of AP. METHODS: AP was induced by sodium taurocholate in rats (n = 140). First group was left untreated. Group II received 100 mg/kg curcumin daily starting 20 days before AP induction. The rats were allocated into 7 sub-groups (n:5) and were sacrificed at 2, 6, 12, 24, 72, 144 and 288 h following the induction of AP. Blood and pancreatic tissue samples were collected for biochemical and histopathologic evaluations and the assessment of protein and mRNA levels, as well. RESULTS: Curcumin decreased total histopathologic scores in comparison with those of the taurocholate group (P < 0.05). Curcumin increased Caspase-3 activity and decreased trypsin activity, while inhibited nuclear factor-κ (NF-κB) at all time points (P < 0.05) and moreover reduced activator protein-1 (AP-1). Curcumin decreased chemokine (except for 288 h), TNF-α (except for 2 and 24 h), IL-6 (except for 2, 6 and 288 h) and iNOS (except for 144 and 288 h) mRNA levels (P < 0.05). Curcumin serum nitric oxide (NO) (except for 144 and 288 h) levels were reduced, as well. CONCLUSIONS: In conclusion, curcumin reduced tissue injury, trypsin activation and inhibited NF-κB and AP-1. However TNF-α, IL-6 and iNOS and NO were not inhibited at all time points. Therefore no direct correlation was detected in the subgroups between tissue injury, proinflammatory cytokines and oxidative enzymes.

Association of the MEFV gene variations with inflammatory bowel disease in Turkey.

BACKGROUND: Association of NOD2 (CARD15) gene mutations with inflammatory bowel diseases (IBD) is well known. We herein aimed to investigate the role of familial Mediterranean fever-associated MEFV variations in IBD patients as additional regional-specific risk factor. STUDY: One hundred thirty-seven (78 female, 56.9%) IBD patients [62 Crohn's disease (CD), 75 ulcerative colitis (UC)] were enrolled into the study. The diagnosis of all patients was confirmed by colonoscopy, histopathology, and the clinical findings. One hundred one healthy donors' samples were used as healthy controls. All patients were genotyped for the most common E148Q, M608I, M694V, and V726A variations of the MEFV and R702W, G908R, and 1007fs of the NOD2. RESULTS: The overall MEFV variation frequency was found to be higher in the IBD (25.5%) patients (28% in UC, 22.6% in CD) compared with controls (9.9%, P=0.006). This association was stronger with the penetrant exon 10 variations (M694V, M680I, V726A; odds ratio =4.5, P=0.001). Contribution of M694V was higher compared with the other variations (14.5% in CD, 17.3% in UC and 3% in controls, odds ratio =6.039, 95% confidence intervals, 1.7-20.7, P=0.002). The overall frequency of 3 NOD2 variants in the IBD group was not different from that of controls. CONCLUSIONS: The results of this study suggest that the MEFV variations may be an additional susceptibility factor for IBD in certain parts of the world where the carrier rate is high, and the genetic background of the IBD patients may show regional changes.

The association of TNFRSF1A gene and MEFV gene mutations with adult onset Still's disease.

Adult onset Still's disease (ASD) is a systemic inflammatory disorder of unknown etiology. ASD is characterized by fever with unknown etiology, rash, arthritis, and involvement of several organ systems. FMF and TRAPS are two important autoinflammatory diseases which characterized with recurrent inflammatory attacks. We aimed in this study to investigate the MEFV gene and TNFRSF1A gene variations in ASD. Twenty consecutive Turkish ASD patients (14 female and 6 male; mean age 38.45 ± 14; mean disease duration 3.3 ± 2.3; mean age of the disease onset 35.1 ± 14.4) and 103 healthy controls of Turkish origin were analyzed. All ASD patients were genotyped for the 4 MEFV mutations (M694V, E148Q, V726A, M680I) and TNFRSF1A gene exon 2-3 and exon 4-5 by using sequence analysis. The healthy controls are genotyped using PCR-RFLP method for intron 4 variation. The results of MEFV gene mutations screening show an increase in the MEFV mutation rate in ASD group, but it was not significantly different (p = 0.442, OR 1.64, 95 % CI 0.409-6.589). T-C polymorphism (rs1800692) was the only variation in the intron 4 of TNFRSF1A gene that we observed at the ASD patients. The frequency of TT genotype was 15 %, TC: 45 %, and CC: 40 % in ASD patients and the frequencies were 22, 41, and 37 % in healthy controls, respectively. When we analyzed the allele difference between both groups, there was no difference (p = 0.54, OR 1.24, 0.619-2.496-2.654). The variations in MEFV may have role in ASD pathogenesis. Our findings suggest that there is no significant association between ASD and TNFRSF1A variations.

TT polymorphism in rs2165241 and rs1048661 region in lysyl oxidase like-1 gene may have a role in stress urinary incontinence physiopathology.

AIM: In experimental studies, lysyl oxidase like-1 (LOX-L1) (-/-) mice were shown to have similar pelvic floor dysfunction to female rats. LOX-L1 levels in endopelvic fascia decrease as a result of increasing births in women with pelvic prolapse. For these reasons, we investigated the LOX-L1 gene polymorphism, which has an important role in connective tissue and collagenous metabolism in stress urinary incontinence (SUI). MATERIALS AND METHODS: A total of 87 women with SUI who underwent normal vaginal delivery and 87 controls were involved in the study. Single nucleotide gene polymorphisms in LOX-L1's rs1048661, G>T, pArg141Leu, Exon-1 SmaI; rs3825942, C>T, pGly153Asp, Hinf-1 and rs2165241, C>T, Intron-1 BsrI regions were searched. The results were statistically compared as alleles with 3×2 χ(2) -test. RESULTS: A total of 32 (34%) GG, 20 (21%) GT, 42 (45%) TT, 32 (37%) GG, 43 (39%) GT, 21 (24%) TT polymorphisms in rs1048661; 30 (36%) CC, 16 (19%) CT, 37 (45%) TT, 41 (59%) CC, 15 (22%) CT, 13 (19%) TT polymorphisms in rs2165241; and 63 (72%) CC, 21 (24%) CT, 3 (4%) TT; 48 (6%) CC, 22 (30%) CT, 3 (4%) TT polymorphisms in rs3825942 were found in patients and the control group, respectively. In patients, the TT polymorphism in the rs1048661 and rs2165241 region were found to be significant. CONCLUSIONS: The homozygote TT polymorphism in the rs1048661 and rs2165241 region of LOX-L1 gene may be responsible from SUI physiopathology.

The relationship between coronary artery ectasia and eNOS intron 4a/b gene polymorphisms.

BACKGROUND: Little is known about the pathogenesis and genetics of coronary artery ectasia (CAE). We studied eNOS gene intron 4a/b polymorphism in this patient population. METHODS: The study group included 30 patients with non-obstructive CAD besides CAE on coronary angiogram performed due to positive non-invasive diagnostic test results. The control group included 20 patients with normal coronary arteries. Agarose gel electrophoresis was used to identify eNOS gene polymorphisms. RESULTS: Only one coronary vessel was involved in most of the study cohort and the left anterior descending artery (LAD) was the most frequently involved vessel. The frequencies of eNOS gene phenotypes in the CAE group were 3.3% for"aa", 53.3% for"ab" and they were higher than in the control group. However, statistical significance was not reached (chi2 = 5.10, P = 0.08). When compared with the control group the presence of "a" type allele of eNOS gene was significantly more frequent in the CAE group (chi2 = 4.88, P = 0.027). By univariate analysis, eNOS gene polymorphism was correlated with CAE but this significance was attenuated after additional adjustment for potential confounding. CONCLUSION: Patients who have the "a" type allele of the eNOS gene may have an increased risk for CAE.