Mutational screening of SF1 and WNT4 in Tunisian women with premature ovarian failure

Background

WNT4 and SF1 genes play an important role in ovarian development. They constitute coherent candidate genes associated with premature ovarian failure (POF) pathogenesis.

Methods

We sequenced the coding region of WNT4 and SF1 in 55 Tunisian women with POF and 100 healthy controls.

Results

We identified a synonymous variation in WNT4 (c.99G>A, p.Ser33Ser) and a substitution (c.G437C) in SF1 gene inducing G146 to Ala (GGG–GCG) missense mutation. WNT4 (c.99G>A, p.Ser33Ser) was not associated with POF pathology. However, a positive association of SF1 Gly146Ala polymorphism was noted. Gly146Ala minor allele frequency was significantly higher (p = 0.029) in POF patients versus controls and Ala allele containing genotypes (p = 0.005) were positively associated with POF pathology. The carriage of 146Ala allele was also associated with a significant reduction in estradiol plasma levels.

Conclusions

SF1 Gly146Ala polymorphism seems to be associated with POF pathology in the Tunisian population likely by reducing estradiol levels.     

Genetic variants in epoxide hydrolases modify the risk of oligozoospermia and asthenospermia in Han-Chinese population

Objectives

Epoxide hydrolases are involved in detoxifying and excreting the environmental chemicals, which are associated with decreased semen quality and male infertility. We hypothesized that polymorphisms in epoxide hydrolases may be associated with risk of oligozoospermia and asthenospermia.

Design and methods

In this study, 468 fertile controls and 672 idiopathic male infertile patients were recruited. SNPstream and TaqMan assay were used to genotype four single nucleotide polymorphisms in EPHX1 and EPHX2. The semen analysis was performed by computer-assisted semen analysis system.

Results

Our results demonstrated that rs1042064 of EPHX2 was significantly associated with decreased risk of oligozoospermia (OR = 0.65, 95% CI: 0.44–0.98) and asthenospermia (OR = 0.66, 95% CI: 0.46–0.94).

Conclusions

Our results provided evidence that genetic variants in epoxide hydrolases may modify the risk of oligozoospermia and asthenospermia in Han-Chinese population.     

The treatment of paravertebral malignant mesenchymal tumor pain with cryoablation

Objective

The purpose of this study was to evaluate the feasibility, safety, and efficacy of cryoablation to treat pain from paravertebral malignant mesenchymal tumors.

Method

Cryoablation was performed on 15 patients who suffer from unresectable painful paravertebral malignant mesenchymal tumors and whose pain was poorly controlled by conventional treatment methods. The sizes of the tumors varied from 3 to 20 cm. The patients’ pain at baseline before the cryoablation and the pain they felt 1 day, 1 week, 1 month, and 3 months after the cryoablation were assessed respectively by the Brief Pain Inventory (BPI).

Result

BPI scores are divided into two categories: the influence of pain and the severity of pain. Both results showed a decline after the cryoablation. The evaluation score of pain severity decreased significantly (P = 0.001, P = 0.031) on the observation of 1 day and 1 month after the cryoablation; that of pain influence decreased significantly (P = 0.016, P = 0.036) in the cases of 1 day and 1 week after cryoablation. Two patients (13.33%) had mild complications, but no serious complications occurred.

Conclusion

Cryoablation is a low risk, well-tolerated topical treatment for the pain of patients with unresectable paravertebral malignant mesenchymal tumor.     

CHK2 1100delC,IVS2 + 1G>A and I157T mutations are not present in hepatocellular cancer cases from a Turkish population

Aim

The cell cycle checkpoint kinase 2 (CHK2) protein participates in the DNA damage response in many cell types. Germline mutations in CHK2 (1100delC, IVS2 + 1G>A and I157T) have been associated with a range of cancer types. This study aimed to investigate whether CHK2 1100delC, IVS2 + 1G>A and I157T mutations play an important role in the development of hepatocellular carcinoma (HCC) in a Turkish population.

Methods

A total of 165 hepatocellular cancer cases and 446 cancer-free controls were genotyped for CHK2 mutations by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-polymerase chain reaction (AS-PCR) methods.

Results

We did not find CHK2 1100delC, IVS2 + 1G>A and I157T mutations in any of 611 Turkish subjects.

Conclusion

Our results demonstrate for the first time that CHK2 1100delC, IVS2 + 1G>A and I157T mutations have not been a genetic susceptibility factor for HCC in the Turkish population. Overall, our data suggests that genotyping of CHK2 mutations in clinical settings in the Turkish population should not be recommended. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins.     

Effects of varying tissue sizes on the efficiency of baboon ovarian tissue vitrification

Objective

The aim of this study was to detect the effects of varying tissue sizes on the efficiency of baboon ovarian tissue vitrification.

Study design

The percentages of morphologically normal primordial follicles and the follicles expressing bax protein in ovarian tissues after vitrification–warming were measured. Besides, the 17-β estradiol levels in the culture supernatants were measured.

Results

The percentages of morphologically normal primordial follicles in vitrified–warmed ovarian tissues slicing in 0.5–1.5 mm in length and wide, and 1.0 mm in thickness were significantly higher than those slicing in 2.0 mm in length and wide, and 1.0 mm in thickness. Moreover, the follicles expressing bax protein in vitrified–warmed ovarian tissues slicing in 0.5–1.5 mm in length and wide, and 1.0 mm in thickness were significantly lower than those slicing in 2.0 mm in length and wide, and 1.0 mm in thickness. The 17-β estradiol levels in the culture supernatants slicing in 1.0–1.5 mm in length and wide, and 1.0 mm in thickness were significantly higher than those slicing in 0.5 mm or 2.0 mm in length and wide, and 1.0 mm in thickness.

Conclusions

Cortex piece slicing in 1.0–1.5 mm in length and wide, and 1.0 mm in thickness is suitable for baboon ovarian vitrification.     

Association between interleukin 4 gene intron 3 VNTR polymorphism and recurrent aphthous stomatitis in a cohort of Turkish patients

Objective

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases, with a multifactorial etiopathogenesis, an interaction between predisposing factors and/or systemic conditions and immunological components in genetically predisposed subjects. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. The purpose of the present study was to investigate a possible association between the functional interleukin 4 (IL4) VNTR genetic polymorphism and RAS in a sample of Turkish patients.

Methods

The study included 145 unrelated patients with a clinical diagnosis of RAS and 150 unrelated healthy controls. Genomic DNA was isolated and IL4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers.

Results

The distribution of genotype and allele frequencies of IL4 gene intron 3 VNTR polymorphism was statistically different between RAS patients and control group (p < 0.0001 and p < 0.0001, respectively) P2P2 genotype and P2 allele were also found to be protective with a lower risk for susceptibility to RAS (p < 0.0001).

Conclusion

The results of this study suggest that intron 3 VNTR polymorphism in the IL4 gene is associated with RAS susceptibility in Turkish population.     

Interaction between gene A-positive Helicobacter pylori and human leukocyte antigen II alleles increase the risk of Graves disease in Chinese Han population: An association study

Objective

The current study explored the correlation of Helicobacter pylori and the polymorphisms of human leukocyte antigen II (HLA-II) alleles with Graves disease (GD).

Methods

A total of 216 patients with GD were recruited. 102 healthy volunteers constituted the control group. Levels of H. pylori immunoglobulin G (IgG) antibodies and H. pylori cytotoxin-associated gene A (CagA) IgG antibodies were detected using enzyme-linked immunosorbent assays. Molecular typing of the HLA-II alleles was conducted using polymerase chain reaction with sequence specific primers.

Results

H. pylori, particularly CagA-positive strains, HLA-DQA1*0201, and HLA-DQA1*0501 were associated with GD (P = 0.015, OR = 1.811; P = 0.000, OR = 3.085; P = 0.000, OR = 0.315; and P = 0.004, OR = 2.844, respectively). Patients with CagA-positive H. pylori and negative HLA-DQA1*0201 or positive HLA-DQA1*0501 were more likely exposed to GD compared with those with only one of these indices.

Conclusion

CagA-positive H. pylori, negative HLA-DQA1*0201, or positive HLA-DQA1*0501 may increase the risk of GD.     

Genetic variants in selenoprotein P plasma 1 gene (SEPP1) are associated with fasting insulin and first phase insulin response in Hispanics

Context

Insulin resistance is not fully explained on a molecular level, though several genes and proteins have been tied to this defect. Knockdowns of the SEPP1 gene, which encodes the selenoprotein P (SeP) protein, have been shown to increase insulin sensitivity in mice. SeP is a liver-derived plasma protein and a major supplier of selenium, which is a proposed insulin mimetic and antidiabetic agent.

Objective

SEPP1 single nucleotide polymorphisms (SNPs) were selected for analysis with glucometabolic measures.

Participants and measures

The study included1424 Hispanics from families in the Insulin Resistance Atherosclerosis Family Study (IRASFS). Additionally, the multi-ethnic Insulin Resistance Atherosclerosis Study was used. A frequently sampled intravenous glucose tolerance test was used to obtain precise measures of acute insulin response (AIR) and the insulin sensitivity index (S_I).

Design

21 SEPP1 SNPs (tagging SNPs (n = 12) from HapMap, 4 coding variants and 6 SNPs in the promoter region) were genotyped and analyzed for association.

Results

Two highly correlated (r² = 1) SNPs showed association with AIR (rs28919926; Cys368Arg; p = 0.0028 and rs146125471; Ile293Met; p = 0.0026) while rs16872779 (intronic) was associated with fasting insulin levels (p = 0.0097). In the smaller IRAS Hispanic cohort, few of the associations seen in the IRASFS were replicated, but meta-analysis of IRASFS and all 3 IRAS cohorts (N = 2446) supported association of rs28919926 and rs146125471 with AIR (p = 0.013 and 0.0047, respectively) as well as rs7579 with S_I (p = 0.047).

Conclusions

Overall, these results in a human sample are consistent with the literature suggesting a role for SEPP1 in insulin resistance.     

Transferrin receptor-1 iron-acquisition pathway — Synthesis,kinetics, thermodynamics and rapid cellular internalization of a holotransferrin–maghemite nanoparticle construct

Background

Targeting nanoobjects via the iron-acquisition pathway is always reported slower than the transferrin/receptor endocytosis. Is there a remedy?

Methods

Maghemite superparamagnetic and theragnostic nanoparticles (diameter 8.6 nm) were synthesized, coated with 3-aminopropyltriethoxysilane (NP) and coupled to four holotransferrin (TFe₂) by amide bonds (TFe₂–NP). The constructs were characterized by X-ray diffraction, transmission electron microscopy, FTIR, X-ray Electron Spectroscopy, Inductively Coupled Plasma with Atomic Emission Spectrometry. The in-vitro protein/protein interaction of TFe₂–NP with transferrin receptor-1 (R1) and endocytosis in HeLa cells were investigated spectrophotometrically, by fast T-jump kinetics and confocal microscopy.

Results

In-vitro, R1 interacts with TFe₂–NP with an overall dissociation constant K_D = 11 nM. This interaction occurs in two steps: in the first, the C-lobe of the TFe₂–NP interacts with R1 in 50 μs: second-order rate constant, k₁ = 6 × 10¹⁰ M^− 1 s^− 1; first-order rate constant, k_− 1 = 9 × 10⁴ s^− 1; dissociation constant, K_1d = 1.5 μM. In the second step, the protein/protein adduct undergoes a slow (10,000 s) change in conformation to reach equilibrium. This mechanism is identical to that occurring with the free TFe₂. In HeLa cells, TFe₂–NP is internalized in the cytosol in less than 15 min.

Conclusion

This is the first time that a nanoparticle–transferrin construct is shown to interact with R1 and is internalized in time scales similar to those of the free holotransferrin.

General significance

TFe₂–NP behaves as free TFe₂ and constitutes a model for rapidly targeting theragnostic devices via the main iron-acquisition pathway.     

Association between resistin + 299A/A genotype and nonalcoholic fatty liver disease in Chinese patients with type 2 diabetes mellitus

Objective

To investigate the relationship between the resistin intronic + 299G/A polymorphism and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).

Methods

We selected 738 T2DM patients, including 395 with NAFLD and 343 without fatty liver disease, as well as 279 healthy control individuals, and analyzed their resistin + 299G/A polymorphism genotype by polymerase chain reaction–restriction fragment length polymorphism.

Results

Plasma resistin levels in T2DM patients with NAFLD were at the highest (P < 0.05). The frequency of AA genotype at the + 299 site of the resistin gene in patients with concurrent T2DM combined with NAFLD was significantly different from that in the control (P < 0.05). The AA genotype was found to be associated with a 1.80-fold increased risk for T2DM combined with NAFLD, 2.05-fold increased risk for obesity and 2.37-fold increased risk for obesity of abdominal type compared to the GG (P < 0.05, respectively). The multivariate non-conditional logistic regression model analysis further shows that the AA genotype is a risk factor for the development of NAFLD in T2DM patients (OR, 2.32; 95% CI, 1.05–4.68; P < 0.05).

Conclusion

The resistin + 299AA genotype may be associated with increases in the risk of the NAFLD development in T2DM patients.     

Meta-analysis of genetic association of chromosome 9p21 with early-onset coronary artery disease

Purpose

A number of studies reported on associations of single nucleotide polymorphisms (SNPs) present in chromosome 9p21 with early-onset coronary artery disease (CAD). The present study was then undertaken to perform a meta-analysis of all the results published to date.

Methods

All studies of the 9p21 association with early-onset CAD that were published between 2007 and 2012 were retrieved from the PubMed database. RevMan 5.0 software was used to perform meta-analysis of the data that fulfilled the criteria for our meta-analysis. The effect size of four SNPs in the 9p21 region on early-onset CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI).

Results

A total of 7123 subjects from 7 case–control studies were genotyped. Meta-analysis demonstrated disease association for rs2383207 (OR = 0.79, 95% CI 0.71–0.88, P < 0.0001), rs2383206 (OR = 1.17, 95% CI 1.10–1.25, P < 0.00001), rs10757278 (OR = 1.28, 95% CI 1.15–1.42, P < 0.00001), and rs10757274 (OR = 1.17, 95% CI 1.08–1.33, P = 0.02).

Conclusion

Genetic variation in the chromosome 9p21 region may contribute to the etiology of early-onset CAD although their effect size is rather small.     

bFGF induces changes in hyaluronan synthase and hyaluronidase isoform expression and modulates the migration capacity of fibrosarcoma cells

Background

Hyaluronan (HA) a glycosaminoglycan, is capable of transmitting extracellular matrix derived signals to regulate cellular functions. In this study, we investigated whether the changes in HT1080 and B6FS fibrosarcoma cell lines HA metabolism induced by basic fibroblast growth factor (bFGF) are correlated to their migration.

Methods

Real-time PCR, in vitro wound healing assay, siRNA transfection, enzyme digestions, western blotting and immunofluorescence were utilized.

Results

bFGF inhibited the degradation of HA by decreasing hyaluronidase-2 expression in HT1080 cells (p = 0.0028), increased HA-synthase-1 and -2 expression as we previously found and enhanced high molecular weight HA deposition in the pericellular matrix. Increased endogenous HA production (p = 0.0022) and treatment with exogenous high molecular weight HA (p = 0.0268) correlated with a significant decrease of HT1080 cell migration capacity. Transfection with siHAS2 and siHAS1 showed that mainly HAS1 synthesized high molecular weight HA regulates HT1080 cell motility. Induced degradation of the HA content by hyaluronidase treatment and addition of low molecular weight HA, resulted in a significant stimulation of HT1080 cells' motility (p < 0.01). In contrast, no effects on B6FS fibrosarcoma cell motility were observed.

Conclusions

bFGF regulates, in a cell-specific manner the migration capability of fibrosarcoma cells by modulating their HA metabolism.HA metabolism is suggested to be a potential therapeutic target in fibrosarcoma.     

Association of heat shock protein70-2 (HSP70-2) gene polymorphism with coronary artery disease in an Iranian population

Background

Coronary artery disease (CAD) is an inflammatory process and a major cause of mortality and morbidity. The (heat shock protein70-2) HSP70-2 gene is reported to be associated with coronary artery disease possibly by affecting the regulation of pro-inflammatory cytokines such as TNF-α. The association between CAD and the HSP70-2 gene + 1267A>G polymorphism has been studied in some populations but there are no data about this association in the Iranian population.

Aim

We have investigated the association between the HSP70-2 gene + 1267A>G polymorphism and angiographically defined CAD within an Iranian population.

Methods

We determined the presence of the HSP70-2 gene + 1267A>G polymorphism in 628 patients with CAD and 307 healthy individuals using PCR-RFLP. Of the patients, 433 (68%) had > 50% stenosis (CAD +) and the remaining 195 patients had < 50% stenosis (CAD −), based on coronary angiography. Angiogram positive patients were subdivided into three groups: those with single (n = 113), double (n = 134), and triple vessels (n = 186) disease.

Results

A significant higher frequency of AG + GG genotypes (G allele carriers) was observed in angiogram positive and angiogram negative groups compared to controls in a dominant analysis model of the HSP70-2 gene + 1267A>G position (51.2 vs. 43.2, P = 0.002, OR = 1.37) (51.0 vs. 43.2, P = 0.01, OR = 1.37). The allele frequency of the HSP70-2 G was also significantly higher in angiogram positive and angiogram negative groups compared to the control group (51.2 vs. 43.2, P = 0.002, OR = 1.37) (51.0 vs. 43.2, P = 0.01, OR = 1.37).

Conclusion

These results suggest that HSP70-2 + 1267 polymorphism may influence the risk of CAD in Iranian population, however further studies are needed to clarify the role of other HSP70-2 gene polymorphisms in the pathogenesis of the CAD.     

Polymorphisms of folate metabolism-related genes and survival of patients with colorectal cancer in the Korean population

Background

5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1). We hypothesized that polymorphisms in the genes encoding these proteins would be associated with CRC patient survival.

Patients and methods

We genotyped the following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS 1494del6, MTHFR 677C > T and 1298A > C, and RFC1 − 43T > C, 80G > A, and 696C > T. Using Kaplan–Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between these polymorphisms and overall survival (OS).

Results

The combined TS 1494 0bp6bp + 6bp6bp genotype was associated with reduced OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the RFC1 − 43CC and 80AA genotypes were associated with favorable OS.

Conclusions

Our data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in Korean patients. Further studies are needed to verify these findings.     

Elevated CpG island methylation of GCK gene predicts the risk of type 2 diabetes in Chinese males

Background

The GCK gene encodes hexokinase 4, which catalyzes the first step in most glucose metabolism pathways. The purpose of our study is to assess the contribution of GCK methylation to type 2 diabetes (T2D).

Methods and results

GCK methylation was evaluated in 48 T2D cases and 48 age- and gender-matched controls using the bisulphite pyrosequencing technology. Among the four CpG sites in the methylation assay, CpG4 and the other three CpGs (CpG1-3) were not in high correlation (r < 0.5). Significantly elevated methylation levels of GCK CpG4 methylation were observed in T2D patients than in the healthy controls (P = 0.004). A breakdown analysis by gender indicated that the association between CpG4 methylation and T2D was specific to males (P = 0.002). It is intriguing that another significant male-specific association was also found between GCK CpG4 methylation and total cholesterol (TC) concentration (r = 0.304, P = 0.036).

Conclusion

Our results showed that elevated GCK CpG4 methylation might suggest a risk of T2D in Chinese males. Gender disparity in GCK CpG4 methylation might provide a clue to elaborate the pathogenesis of T2D.     

Association study of polymorphisms in the receptor for advanced glycation end-products (RAGE) gene with susceptibility and prognosis of heart failure

Background

Functional polymorphisms in the receptor for advanced glycation end-products (RAGE) gene have been implicated in several vascular diseases. However, to date, no study investigated the association of RAGE polymorphisms with heart failure (HF).

Objective

In this study we tested the hypothesis that the 63-bp insertion/deletion, the − 374T > A (rs1800624) and the − 429T > C (rs1800625) polymorphisms in the RAGE gene might be associated with susceptibility to HF and could predict all-cause mortality in Brazilian outpatients with left ventricular systolic dysfunction.

Methods

A total of 273 consecutive HF patients (196 Caucasian- and 77 African-Brazilians) and 334 healthy blood donors (260 Caucasian- and 74 African-Brazilians) were enrolled in a tertiary care university hospital. Genotyping of RAGE polymorphisms was done by polymerase chain reaction (PCR) or PCR followed by enzyme restriction analysis.

Results

The allele, genotype and haplotype frequencies of − 374T > A and − 429T > C polymorphisms were not significantly different between HF patients and healthy blood donors in both ethnic groups. However, among African-Brazilians, the frequency of carriership of the del allele was lower in HF patients than in blood donors (2.6% vs 12.2%, respectively, p = 0.008). Patients were followed-up for a median of 38 months and the survival analysis did not reveal a consistent association between RAGE polymorphisms and all-cause death in both ethnic groups.

Conclusion

The − 374T > A and − 429T > C polymorphisms in the RAGE gene were not associated with the susceptibility and prognosis of HF. Notwithstanding, the 63-bp ins/del polymorphism might be involved in the susceptibility to HF in African-Brazilians.     

The impact of GGH -401C > T polymorphism on cisplatin-based chemoradiotherapy response and survival in cervical cancer

Aims

Cervical cancer is the third most frequent cancer in women worldwide, mostly treated with cisplatin-based chemoradiotherapy. Since it is known that folate metabolism might interfere with cisplatin effectiveness, we intended to study the influence of the Gamma Glutamyl Hydrolase -401C > T polymorphism in treatment response in cervical cancer.

Methods

We retrospectively reviewed the clinical data of 167 patients with bulky cervical cancer submitted to cisplatin-based chemoradiotherapy. The genotypes of GGH -401C > T SNP were determined by real-time PCR and statistical analysis was performed by χ² test and survival analysis.

Results

The genotypes of GGH-401C > T were significantly associated with the response to platinum-based chemoradiotherapy. Treatment response was higher in patients carrying the CC genotype, who presented a significant increased chance of treatment response (survival time in months/genotype: 91 for CC Vs 72 for CT/TT; p = 0.035, log rank test). A Cox regression analysis accordingly showed that the presence of the T allele was significantly linked to a worse treatment response (HR = 3.036; CI 95% 1.032-8.934, p = 0.044).

Conclusions

The results of our study suggested the potential interest of GGH -401C > T as a predictive factor of the outcome of cervical carcinoma treated with cisplatin-based chemoradiotherapy.     

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) +1858 C>T gene polymorphism in Egyptian cases with rheumatoid arthritis

Background

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The gene encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been reported to be associated with RA in several populations.

Objectives

This work aimed at assessing the association of PTPN22 +1858 C>T gene polymorphism with the susceptibility, activity and severity of RA in Egyptian subjects.

Subjects and methods

This study included 112 unrelated RA patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for PTPN22 +1858 C>T (rs2476601) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Cases showed significantly higher PTPN22 +1858 T allele carriage rate (CT + TT genotypes) compared to controls (34.8% vs. 8.2%, OR = 5.98, 95% CI = 2.81–12.73, p < 0.001). Also the frequency of the PTPN22 +1858 T allele was significantly higher among cases compared to controls (18.7% vs. 4.5%, OR = 4.89; 95% CI = 2.45–9.76, p < 0.001). Cases positive to the PTPN22 T allele (CT + TT genotypes) showed no significant difference from those with the CC genotype regarding clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p = 0.04).

Conclusions

This study is a confirmatory evidence of the association of the PTPN22 +1858 T allele with susceptibility and functional disability of RA in Egyptian subjects.     

Cerebrospinal fluid light and heavy neurofilaments in neuromyelitis optica

Background

Axonal injury is the correlate of disease progression in NMO and MS. Neurofilament (Nf) belongs to neuron specific intermediate filaments located in axons. Nf protein subunits are potential biomarkers in cerebrospinal fluid (CSF) for acute axonal injury. However, whether CSF NfH and NfL levels are elevated in NMO patients has remained unclear.

Methods

Nf light subunit (NfL) and Nf heavy subunit NfH in cerebrospinal fluid were measured by enzyme-linked immunosorbent assay (ELISA) in NMO (n = 32), MS (n = 25), and other non-inflammatory neurological disease patients (OND, n = 18).

Results

CSF pNf-H levels were increased in the NMO patients compared with OND patients (p = 0.001). CSF NfL levels in the NMO patients were also higher compared with MS patients (p = 0.001), and OND patients (p = 0.000001). When comparing NfL levels between MS and OND patients, there also significant differences (p = 0.0003). NMO and MS patients revealed a trend to an increased disability with increased CSF NfL during relapse (NMO: p = 0.006; MS: p = 0.017). There is positive relationship between CSF pNf-H and disability of MS patients (p = 0.041).

Conclusions

CSF levels of NfL are increased in NMO patients and reflect the disease severity in NMO.