Investigation of CD40 gene rs4810485 and rs1883832 mutations in patients with recurrent aphthous stomatitis

ObjectivesRecurrent aphthous stomatitis (RAS) is a common painful disorder affecting oral health, mucosa and overall quality of life. The etiopathogenesis of RAS remains unclear. RAS shows a large genetic diversity among the patients. In present study, we investigated whether CD40 gene rs4810485 and rs1883832 are associated with RAS and its clinical findings in Turkish patients.Materials and methodsGenomic DNA obtained from 387 individuals (160 patients with RAS and 227 healthy controls) were used in the study. CD40 gene rs4810485 and rs1883832 mutations were determined by using polymerase chain reaction with the specific primers.ResultsThere was no statistically significant difference between the groups with respect to genotype and allele distribution (p > 0.05, OR 0.94, 95% CI 0.70–1.28, OR 1.01 95% CI 0.75–1.37, respectively). Additionally, there was no statistically significant difference in the combined genotype analysis of CD40 gene rs4810485 and rs1883832 mutations (p > 0.05).ConclusionsAccording to our results, we found that CD40 gene mutations are not associated with RAS. We are convinced that CD40 gene mutations do not predispose to develop RAS in Turkish population. To our knowledge, this is the first study regarding CD40 gene rs4810485 and rs1883832 mutations investigated in RAS patients.     

Different ovarian stimulation protocols for women with diminished ovarian reserve

Purpose To review the available treatments for women with significantly diminished ovarian reserve and assess the efficacy of different ovarian stimulation protocols. Methods Literature research performed among studies that have been published in the Pubmed, in the Scopus Search Machine and in Cohrane database of systematic reviews. Results A lack of clear, uniform definition of the poor responders and a lack of large-scale randomized studies make data interpretation very difficult for precise conclusions. Optimistic data have been presented by the use of high doses of gonadotropins, flare up Gn RH-a protocol (standard or microdose), stop protocols, luteal onset of Gn RH-a and the short protocol. Natural cycle or a modified natural cycle seems to be an appropriate strategy. Low dose hCG in the first days of ovarian stimulation has promising results. Molecular biology tools (mutations, single nucleotide polymorphisms (SNPs)) have been also considered to assist the management of this group of patients. Conclusions The ideal stimulation for these patients with diminished ovarian reserve remains a great challenge for the clinician, within the limits of our pharmaceutical quiver. Stimulation protocols commonly used for women with significantly diminished ovarian reserve.     

A novel ferroportin mutation in a Canadian family with autosomal dominant hemochromatosis

We report a new mutation, Asn185Asp, in exon 6 of the ferroportin gene (FPN1) in 15 members of three successive generations of a Canadian family of Scandinavian origin with autosomal dominant hemochromatosis. Hyperferritinemia with low transferrin saturation was noted in younger family members, seven of whom were aged 20 years or less at the time of diagnosis. In those individuals first diagnosed with hemochromatosis in later life, marked hyperferritinemia was accompanied by high transferrin saturation. In contrast to the phenotype of high ferritin with low saturation first reported for ferroportin disease, this family demonstrates a phenotype of iron indices that varies with age.     

乙型肝炎病毒X基因变异与隐匿性感染的关系

隐匿性HBV感染指患者血清HBsAg阴性,而血清和(或)肝组织HBV DNA阳性,其发生机制仍未明了.目前,对HBV基因变异的研究大多集中在S基因,而X基因是病毒复制的重要调节区,是转录、反转录和正链合成的起点,此处变异可能会影响到病毒的转录和复制,但由于X基因结构和功能的复杂性,目前对其变异与隐匿性HBV感染的关系研究相对较少.此文就HBV X基因变异对隐匿性HBV感染的发生和影响进行综述.     

Targeting c-KIT,PDGFR in cancer of unknown primary: a screening study for molecular markers of benefit

Aims In view of available targeted therapies, we investigated the presence of c-kit, PDGFR gene mutations and protein expression in cancer of unknown primary (CUP) in order to study their contribution in pathogenesis, their prognostic value and potential as therapeutic targets. Methods Mutations in hot spots c-kit exon 11 and PDGFR exons 12 and 18 were studied in paraffin-embedded tumour samples from 50 patients with CUP by means of PCR-based single-strand conformational polymorphism and protein expression by means of streptavidin-biotin immunoperoxidase assays. Molecular markers were screened for possible correlations with patient outcome. Results No shifted band was detected in any of the polyacrylamide gel electrophoreses, indicating absence of c-kit exon 11 and PDGFR exon 12, 18 mutations. Immunohistochemical analysis in 37 tumours revealed positive membranous CD117 expression in 30 samples (81%) of which five exhibited strong (+3), four moderate (+2) and 21 weak (+1) staining. PDGFRa protein staining was seen in 15 out of 30 (50%) cases, mostly weak (13) and rarely moderate (1) or strong (1). The expression of KIT or PDGFRa protein did not correlate with the clinical outcome of the patients in our cohort. Conclusions In a moderate-sized CUP patient cohort, KIT or PDGFRa protein overexpression is rare, does not have gross prognostic significance for survival and is not associated with presence of activating mutations.     

The Trp-Stop and Trp-Gly mutations in the LDL receptor gene: common causes of familial hypercholesterolemia in Denmark

Mutations in the gene for the low density lipoprotein (LDL) receptor cause the autosomal dominant disease familial hypercholesterolemia (FH), the prevalence of which is about 0.2% in most populations. By PCR-SSCP analysis and direct sequencing, we identified the receptor-negative Trp²³-Stop LDL receptor mutation (FH Cincinnati-5) in 10 of 63 FH probands and the receptor-defective Trp⁶⁶-Gly LDL receptor mutation (FH French Canadian-4) in another 10 of the 63 FH probands. These two mutations thus account for 30% of diagnosed FH families in Denmark. Comparison of the mean lipid concentrations (unadjusted and adjusted for age), including serum total cholesterol and LDL-cholesterol, showed no significant differences between the two groups of FH heterozygote probands (cholesterol: 10.7 mmol/l vs. 10.7 mmol/l) and between the probands and 16 and 22 non-proband family members with the Trp²³-stop (cholesterol: 10.1 mmol/l) and Trp⁶⁶-Gly (cholesterol: 10.7 mmol/l) mutations, respectively.     

Canalopatias cardíacas: o papel das mutações nos canais de sódio

Introduction and objectives

The importance of sodium channels for the normal electrical activity of the heart is emphasized by the fact that mutations (inherited or de novo) in genes that encode for these channels or their associated proteins cause arrhythmogenic syndromes such as the Brugada syndrome and the long QT syndrome (LQTS). The aim of this study is to conduct a review of the literature on the mutations in the sodium channel complex responsible for heart disease and the implications of a close relationship between genetics and the clinical aspects of the main cardiac channelopathies, namely at the level of diagnosis, risk stratification, prognosis, screening of family members and treatment.

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics

Mutations in the glucokinase (GCK) gene are considered to be a possible cause of maturity-onset diabetes of the young. The purpose of this study was to evaluate the contribution of this gene to the development of post-renal transplantation diabetes mellitus (PTDM). Identification of the GCK mutation was attempted in 58 selected renal allograft recipients with PTDM and 45 normal controls. The exons in the GCK gene were examined using polymerase chain reaction (PCR), followed by an analysis of single-stranded DNA conformational polymorphism (SSCP). The abnormal bands were then confirmed by DNA sequencing analysis. The family members of the patients affected with GCK mutation were also examined. Two of the 58 PTDM patients (3.4%) were found to have GCK mutations. One had the mutation on exon 5 and the other on intron 7. One control subject had the mutation on intron 9. The mutation on exon 5 was identified as a substitution of CCT (proline) for CTT (leucine) at codon 164, which has never been reported before. The family members of the PTDM patient with a mutation on exon 5 were analyzed by PCR, followed by SSCP, and two of them had the same mutation. The abnormal band seen on SSCP analysis of exon 7 was identified as the C→T substitution at the 39th nucleotide in intron 7. Two of the family members also displayed the same bands on the SSCP. One of the 45 normal controls had a known polymorphism located at the 8th nucleotide in intron 9. We found a GCK mutation on the exon in subjects with PTDM and we speculate that this mutation may be one of the possible contributing factors of PTDM, although variations of the GCK gene are not common causes of PTDM.     

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with asymptomatic malaria in a rural community in Burkina Faso

ObjectiveTo investigate 4 combinations of mutations responsible for glucose-6-phosphate dehydrogenase (G6PD) deficiency in a rural community of Burkina Faso, a malaria endemic country.MethodsTwo hundred individuals in a rural community were genotyped for the mutations A376G, G202A, A542T, G680T and T968C using TaqMan single nucleotide polymorphism assays and polymerase chain reaction followed by restriction fragment length polymorphism.ResultsThe prevalence of the G6PD deficiency was 9.5% in the study population. It was significantly higher in men compared to women (14.3% vs 6.0%, P=0.049). The 202A/376G G6PD A- was the only deficient variant detected. Plasmodium falciparum asymptomatic parasitaemia was significantly higher among the G6PD-non-deficient persons compared to the G6PD-deficient (P<0.001). The asymptomatic parasitaemia was also significantly higher among G6PD non-deficient compared to G6PD-heterozygous females (P<0.001).ConclusionsThis study showed that the G6PD A- variant associated with protection against asymptomatic malaria in Burkina Faso is probably the most common deficient variant.