Association of <Emphasis Type="Italic">Lewis</Emphasis> and <Emphasis Type="Italic">Secretor</Emphasis> gene polymorphisms and <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositivity among Japanese-Brazilians

Background Secretor (Se) and Lewis (Le) genes are involved in the synthesis of Lewis b (Le^b) and type I antigens throughout the body, especially in the epithelial cells of gastric mucosa. Helicobacter pylori can attach to the gastric epithelial cells with the blood group antigen-binding adhesin, which binds to Le^b or H type I carbohydrate structures. In a previous study, a marked association between H. pylori seropositivity and polymorphism of the Se and Le genes was observed among Japanese outpatients of a gastroenterology clinic. The present work aims to investigate the associations between Se and Le gene polymorphisms and H. pylori infection among Japanese-Brazilians.Methods The subjects consisted of 942 healthy volunteer Japanese-Brazilians, who were tested for the presence of anti-H. pylori IgG antibodies and genotyped for Se and Le polymorphisms.Results The sex-age-adjusted odds ratios (aORs) for H. pylori seropositivity were 0.99 for the Sese genotype relative to the SeSe genotype (95% confidence interval [CI], 0.73–1.33), and 1.03 for sese relative to SeSe (95% CI, 0.71–1.48). On the other hand, the aOR for the subjects with the le allele (Lele or lele) relative to the LeLe genotype was 1.48 (95% CI, 1.07–1.79). When the Se and Le genotypes were analyzed in combination according to risk group, no statistically significant association was observed.Conclusions These results are inconsistent with previous work and may have been modulated by an external factor or some other unidentified factor. Japanese-Brazilians are genotypically the same as Japanese, but their lifestyle is adapted to that of Brazil. Further investigations are necessary to clarify this influence on susceptibility to H. pylori infection.     

<Emphasis Type="Italic">Fas/FasL,Bcl2</Emphasis> and <Emphasis Type="Italic">Caspase</Emphasis>-<Emphasis Type="Italic">8</Emphasis> gene polymorphisms in Chinese patients with rheumatoid arthritis

Apoptosis signals are necessary for maintaining homeostasis and an adequate immune response. Dysregulation of apoptosis-related genes in the immune system has an important impact on autoimmune diseases such as rheumatoid arthritis (RA). Thus, we investigated the association between Fas rs2234767 G/A, FasL rs763110 C/T, Bcl2 rs12454712 T/C, Bcl2 rs17757541 C/G, and Caspase-8 rs1035142 G/T polymorphisms and RA susceptibility in a Chinese population. These five single-nucleotide polymorphisms (SNPs) were studied in a Chinese population consisting of 615 patients with RA and 839 controls. Genotyping was performed using a custom-by-design 48-Plex SNP scan TM kit. Furthermore, we undertook a meta-analysis between FasL rs763110 C/T and RA. This study indicated that Fas rs2234767 and Bcl2 rs17757541 polymorphisms were risk factors for RA. No association was observed between FasL rs763110 C/T, Bcl2 rs12454712 T/C, and Caspase-8 rs1035142 G/T polymorphisms and RA in this study. The results of this meta-analysis suggested no significant association between FasL rs763110 C/T and RA. However, stratification analysis of this meta-analysis indicated that FasL rs763110 C/T increased the risk of Caucasian RA patients. In conclusion, this study demonstrated that Fas rs2234767 G/A and Bcl2 rs17757541 T/C polymorphisms might be associated with an increased risk of RA. This meta-analysis revealed that FasL rs763110 C/T was associated with an increased risk of Caucasian RA patients.     

Novel <Emphasis Type="Italic">hMSH</Emphasis>2, <Emphasis Type="Italic">hMSH</Emphasis>6 and <Emphasis Type="Italic">hMLH</Emphasis>1 gene mutations and microsatellite instability in sporadic colorectal cancer

Purpose To detect the hMSH2, hMSH6 and hMLH1 DNA mismatch repair gene mutations and microsatellite instability in somatic colorectal cancer.Patients and methods The mutations of hMSH2, hMSH6, and hMLH1 genes, including microsatellite instability of BAT-26, BAT-40, D2S123, D5S346 and D17S250 were analyzed in 31 patients with colorectal.Results The results revealed that eight cases (25.8%) harbored mutations in DNA mismatch repair genes. Of these, five novel mutations including I237V in exon 4 of hMSH2, ins T at codon 1196 in exon 7 of hMSH6, and ins G at codon 154 in exon 6, N158H in exon 6, and del A at codon 257 in exon 9 of hMLH1 were identified. Moreover, several intronic polymorphisms, including c–g transversion at IVS-1 nt211 + 9 of hMSH2, del T in poly T track at IVS-6 nt3559-5, ATCT duplicate in IVS-7 nt 3642 + 35 and t–g transversion at IVS-10 nt4080 + 185 of hMSH6 were demonstrated in these patients. In addition, seven cases (22.5%) exhibited microsatellite instability (MSI).Conclusion These results suggested that the inactivation of DNA mismatch repair genes and microsatellite instability may play a minor role in somatic colorectal cancer development.     

Elevated expression of the <Emphasis Type="Italic">EZH2</Emphasis> gene in <Emphasis Type="Italic">CALR</Emphasis>-mutated patients with primary myelofibrosis

Primary myelofibrosis (PMF) is one of the BCR/ABL-negative myeloproliferative neoplasms (MPNs), characterized by the diffuse fibrous hyperproliferation, bone marrow osteosclerosis, extramedullary hematopoiesis, and marked splenomegaly. The patients with PMF have an insidious onset, a long duration of clinical course, and the deteriorated quality of life. It has been reported that the CALR gene 9 exon mutations were detected in 25–30% PMF patients, particularly as high as 80% in the JAK2/MPL-negative ones. As the second most common mutation in BCR/ABL-negative MPNs, CALR mutation has been included in the latest World Health Organization (WHO) classification criteria as one of the main diagnostic criteria for both essential thrombocythemia (ET) and PMF. Moreover, the CALR mutations indicated a favorable prognosis, which the mechanism is still under investigation. It was demonstrated that a characterized high expression of EZH2 and SUZ12 in CALR-mutated patients. Taking EZH2 as the research entry point, we initially discussed the mechanism that the CALR-positive patients with PMF exhibited a better prognosis in the current study.     

<Emphasis Type="Italic">T-</Emphasis>Scores and <Emphasis Type="Italic">Z</Emphasis>-Scores

Bone mineral density (BMD) can be measured by a variety of techniques at several skeletal sites. Once measured, the manufacturers’ software uses the BMD to calculate a T-score and/or Z-score. Both T-scores and Z-scores are derived by comparison to a reference population on a standard deviation scale. The recommended reference group for the T-score is a young gender-matched population at peak bone mass, while the Z-score should be derived from an age-matched reference population. T-scores and Z-scores are widely quoted in scientific publications on osteoporosis and BMD studies, and are the values used for DXA diagnostic criteria and current clinical guidelines for the management of osteoporosis. Errors in BMD measurement, differences in reference populations, and variations in calculation methods used, can all affect the actual T-score and Z-score value. Attempts to standardize these values have made considerable progress, but inconsistencies remain within and across BMD technologies. This can be a source of confusion for clinicians interpreting BMD results. A clear understanding of T-scores and Z-scores is essential for correct interpretation of BMD studies in clinical practice.     

Novel mutations in <Emphasis Type="Italic">WWOX</Emphasis>, <Emphasis Type="Italic">RARS2</Emphasis>, and <Emphasis Type="Italic">C10orf2</Emphasis> genes in consanguineous Arab families with intellectual disability

Intellectual disability is a heterogeneous disease with many genes and mutations influencing the phenotype. Consanguineous families constitute a rich resource for the identification of rare variants causing autosomal recessive disease, due to the effects of inbreeding. Here, we examine three consanguineous Arab families, recruited in a quest to identify novel genes/mutations. All the families had multiple offspring with non-specific intellectual disability. We identified homozygosity (autozygosity) intervals in those families through SNP genotyping and whole exome sequencing, with variants filtered using Ingenuity Variant Analysis (IVA) software. The families showed heterogeneity and novel mutations in three different genes known to be associated with intellectual disability. These mutations were not found in 514 ethnically matched control chromosomes. p.G410C in WWOX, p.H530Y in RARS2, and p.I69F in C10orf2 are novel changes that affect protein function and could give new insights into the development and function of the central nervous system.     

Congenital Hyperinsulinism due to mutations in <Emphasis Type="Italic">HNF4A</Emphasis> and <Emphasis Type="Italic">HADH</Emphasis>

Mutations in the HADH and HNF4A genes are rare causes of diazoxide responsive congenital hyperinsulinism (CHI). This chapter details the phenotype known to be associated with mutations in these genes. Additionally, the authors give a brief overview of the role of these genes in glucose physiology and the possible mechanisms of CHI in patients with mutations in these genes.     

<Emphasis Type="Italic">HFE</Emphasis> mutations in heart disease

Given the reported association of cardiac complications with hereditary hemochromatosis and the high carrier frequency of HFE gene mutations in the natural population, it seems reasonable that such mutations might appear more frequently than expected among symptomatic cardiac patients. Thus, H63D, C282Y, and S65C mutations and their possible associations were examined in 477 Caucasian males undergoing coronary angiography. Genotypes were analyzed for differences between ferritin and transferrin levels, coronary artery disease (CAD), cardiomyopathy (CM), and cardiovascular disease (CVD) mortality. No significant differences were found in ferritin levels between those with or without HFE mutations (C282Y P = 0.632, H63D P = 0.765, S65C P = 0.568, and HFE mutation P = 0.568); however, there was a significant difference (P = 0.005) in mean transferrin levels between those with (252 mug/l) and without (275 mug/l) C282Y. No relationship between HFE mutations and CAD (C282Y, P = 0.402; H63D, P = 0.112; S65C, P = 0.170) or CVD death (C282Y, P = 0.560; H63D, P = 0.682; S65C, P = 0.664) was demonstrated using logistic regression. However, an association between S65C and CM was found (odds ratio 4.4; 95% confidence interval 1.3-13.3, P = 0.018). This suggests that the S65C allele may contribute to the development of CM, but that these three HFE mutations do not appear to play a significant role in development of ischemic heart disease.     

<Emphasis Type="Italic">Anisakis</Emphasis> spp. burden in <Emphasis Type="Italic">Trachurus trachurus</Emphasis>

Anisakis is a parasite of marine mammals that uses a great number of fish species as intermediate or paratenic hosts. It is common in commercially important marine fishes and its presence is of great concern for both human health and economic reasons. Horse mackerels (Trachurus trachurus) originated from the Northern Aegean Sea were examined for the presence of Anisakis spp. larvae. The prevalence of Anisakis spp. was found 98.8 %. The number of parasites was significantly related to the host’s length but was not related to the fish gender. The month of sampling affected the size of the fishes and consequently the number of parasites. The length of larvae was not related to the host’s length. The present study resulted in the design of a prediction model for the number of existing parasites in the fish by measuring only its Fixed Length.     

Predominant <Emphasis Type="Italic">porB1A</Emphasis> and <Emphasis Type="Italic">porB1B</Emphasis> genotypes and correlation of gene mutations with drug resistance in <Emphasis Type="Italic">Neisseria gonorrhoeae</Emphasis> isolates in Eastern China

Background  

Variations of porB1A and porB1B genes and their serotypes exist in Neisseria gonorrhoeae isolates from different geographical areas, and some site mutations in the porB1B gene correlate with drug resistance.     

Permanent neonatal diabetes due to activating mutations in <Emphasis Type="Italic">ABCC8</Emphasis> and <Emphasis Type="Italic">KCNJ11</Emphasis>

The ATP-sensitive potassium (K_ATP) channel is composed of two subunits SUR1 and Kir6.2. The channel is key for glucose stimulated insulin release from the pancreatic beta cell. Activating mutations have been identified in the genes encoding these subunits, ABCC8 and KCNJ11, and account for approximately 40% of permanent neonatal diabetes cases. The majority of patients with a K_ATP mutation present with isolated diabetes however some have presented with the Developmental delay, Epilepsy and Neonatal Diabetes syndrome. This review focuses on mutations in the K_ATP channel which result in permanent neonatal diabetes, we review the clinical and functional effects as well as the implications for treatment.     

Early diagnosis of mucopolysaccharidosis III A with a nonsense mutation and two <Emphasis Type="Italic">de novo</Emphasis> missense mutations in <Emphasis Type="Italic">SGSH</Emphasis> gene

Summary An early presentation of heparan N-sulphatase (SGSH) deficiency (mucopolysaccharidosis IIIA, MPS IIIA) with a prominent and isolated hepato-splenomegaly is described. Molecular analysis detected a nonsense mutation (Y40X) and two de novo missense mutations (E300V; Q307P).     

Prosthetic valve endocarditis caused by <Emphasis Type="Italic">Pseudomonas luteola</Emphasis>

Background  

Pseudomonas luteola has been recognized as an uncommon cause of bacteremia and of infections in patients with underlying medical disorders