Association of Thyroid Peroxidase Gene Polymorphisms and Serum Anti- TPO Levels in Egyptian Patients with Autoimmune Hypothyroidism.

BACKGROUND: Thyroid peroxidase (TPO) gene mutation leads to a change in enzyme built structure resulting in the anti-TPO autoantibodies production that may cause thyroid destruction. AIM: To evaluate the association of three single nucleotide polymorphisms (SNPs) of the TPO gene and anti-TPO levels in Egyptian patients with autoimmune hypothyroidism and correlate them with the disease severity. METHODS: Two hundred patients with newly discovered autoimmune hypothyroidism were included in the study (100 with subclinical hypothyroidism and 100 of them with overt hypothyroidism) and 100 healthy individuals as a control group were genotyped by PCR-REFLP. RESULTS: The TT genotype of rs2071400 C/T and the T allele were significantly more frequent in patients with subclinical hypothyroidism and overt hypothyroidism than in the control group. But there were no significant differences in the TT genotype and T allele between subclinical and overt hypothyroidism patients. As regards TPO rs732609 A/C polymorphism, the CC genotype of rs732609 A/C and the C allele were significantly increased in patients with subclinical hypothyroidism and overt hypothyroidism than in controls. There was a significant difference in the CC genotype and C allele between subclinical and overt hypothyroidism patients. Concerning TPO rs1126797 C/T polymorphism, there were no significant differences of genotype or allele frequencies between patients groups and control group. CONCLUSION: We found an association of rs2071400 C/T and rs732609A/C polymorphisms with autoimmune hypothyroidism and correlated anti-TPO levels with different genotypes in hypothyroid patients. Also, we found an association of rs732609A/C polymorphism with the disease severity.

Association of genetic polymorphism of BCL-2 (rs2279115) with susceptibility to HCV-related hepatocellular carcinoma.

Hepatitis C virus (HCV) infection is the main risk factor for chronic hepatitis (CHC), liver cirrhosis, and hepatocellular carcinoma (HCC). B cell lymphoma-2 (BCL-2) prevents apoptosis, and its overexpression could promote cancer cell survival. The purpose of this study is to evaluate the association of Bcl-2 gene polymorphism (rs2279115) and HCV-related HCC susceptibility. Two hundred and seventy individuals included in this case-control were divided into three groups. Group I: It included 90 apparently healthy subjects as control. Group II: It includes 90 patients with chronic HCV hepatitis. Group III: It includes 90 patients with HCC with positive HCV. Bcl-2 gene polymorphism (rs2279115) C > A genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There are significantly higher incidence of CA and AA genotypes in HCV patients with HCC compared with those without HCC (OR 2.3, %CI (1.2-4.6), P = 0.01 and OR 5.7, %CI (2.4-13.8), respectively) and compared with control group (OR 2.9, %CI (1.5-5.8), P = 0.002 and OR 7.1, %CI (2.9-17.4), P < 0.001, respectively), while no significant difference between the control and HCV patients without HCC groups (OR 1.2, %CI (0. 7-2.4), P = 0.48, for CA, and OR 1.2, %CI (0.4-3.3), P = 0.67, for AA).The frequency of A allele was highly significantly overrepresented in the HCC group in comparison to HCV group (53.3% versus 30.6%, P < 0.001) and control group (53.3% versus 27.2%, P < 0.001) but no significant difference (p = 0.49) between control group and HCV patients. This study demonstrated that Bcl-2 gene polymorphism (rs2279115) was associated with increased susceptibility to HCV-related HCC.

Association of vaspin gene expression and its serum level on the risk of ischemic stroke in type 2 diabetic Egyptian patients: Prospective case-control study.

We aimed to evaluate serum vaspin and its gene expression in patients with type 2 diabetes mellitus (T2DM) and to assess the association of serum vaspin and its gene expression with susceptibility of ischemic stroke (IS). The prospective case-control study included 50 healthy individuals in a control group, and 90 patients with and T2DM were stratified into two subgroups: patients with IS and patients without IS. The serum vaspin concentration was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was performed to detect the mRNA expression of vaspin. Serum vaspin and vaspin expression levels were significantly higher in IS compared to the non-IS group. Interestingly, they were positively correlated with other vascular and metabolic risks. Diastolic and systolic blood pressure, as well as hemoglobin A1c cholesterol (HbA1c), were independently correlated with serum vaspin. After adjusting for the traditional risk factors, the logistic regression analysis test was done to evaluate the predictor of IS among T2DM patients; the vaspin expression level was a statistical significance predictor of IS among T2DM patients. In conclusion, the higher levels of serum vaspin and vaspin expression levels in T2DM emphasizes the pivotal role of vaspin serum level and expression in the progression of metabolic and glucose abnormalities, thus, they could be used as biomarkers of IS.

Genetic polymorphism of methylenetetrahydrofolate reductase is associated with insulin resistance in Egyptian women with polycystic ovary syndrome.

BACKGROUND: A common polymorphism (677C to T; Ala to Val) in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased specific MTHFR activity and elevation of homocysteine. The present study aimed to investigate the association between a single nucleotide polymorphism (SNP) in the MTHFR 677C>T gene and insulin resistance in women with polycystic ovary syndrome (PCOS). METHODS: Two-hundred patients with PCOS were included in this case-control study: 100 patients with insulin resistance and 100 patients without insulin resistance were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The TT genotype for the MTHFR 677C>T polymorphism was significantly more frequent in PCOS patients with insulin resistance than in PCOS patients without insulin resistance (19% versus 6%, p = 0.002), whereas there was no significant difference between both groups for CT and there was a statistically significant increase in the T allele in PCOS patients with insulin resistance compared to PCOS patients without insulin resistance (p = 0.002, odds ratio = 1.95 and 95% confidence interval = 1. 29-2.93). Regarding the relationship between MTHFR 677C>T genotypes and the characteristics of insulin resistance in PCOS patients, we found that there was no significant difference in age, waist-hip ratio and total testosterone between the different genotypes of the MTHFR 677C>T polymorphism. The mean values for body mass index and the Homeostatic Model Assessment of Insulin Resistance were significantly higher in the TT genotype of MTHFR 677C>T compared to the CC genotype in PCOS patients with insulin resistance (p < 0.001). CONCLUSIONS: We have demonstrated an association of the MTHFR 677C>T gene polymorphism with insulin resistance in Egyptian women with PCOS.

Glutathione S-Transferase M1 and T1 Gene Polymorphisms and the Outcome of Chronic Hepatitis C Virus Infection in Egyptian Patients.

We analysed the distribution of GSTM1 and GSTT1 gene polymorphisms in Egyptian patients with chronic hepatitis C, and investigated their relationship to the clinical outcome of chronic hepatitis C virus (HCV) infection. This study included 169 patients with chronic HCV infection and 145 healthy and matched controls.GSTM1 and GSTT1 polymorphisms were genotyped by multiplex polymerase chain reaction. Individual GSTM1 null and GSTT1 null genotypes were more frequent in patients versus control subjects [OR, 4 (95% CI, 2.5-6.4); P ˂ 0.001] and [OR, 1.7 (95% CI, 1.1-2.6); P = 0.025], respectively. The patient group showed a higher frequency of the combined GSTM1/GSTT1 double-null genotype than the control group [OR, 1.8 (95% CI, 1.1-2.9); P = 0.016]. The distribution frequencies of the combined GSTM1/GSTT1 double-null genotype were significantly different [OR, 0.5 (95% CI, 0.25-0.99); P = 0.049] between F0-F3 and F4. There were no significant differences between the two groups with regard to other genotypes. The combined GSTM1/GSTT1 double-null genotype was significantly increased in Child-Pugh C patients in comparison to Child-Pugh A+B (P = 0.02). There was no significant difference between different classes with regard to other genotypes. In conclusion, we identified an association between the combined GSTM1/GSTT1 double-null genotype and advanced liver fibrosis and outcome of chronic HCV infection in Egyptian patients.

Circulating Dickkopf-1 in hypoxic ischemic neonates.

OBJECTIVE: The current study aimed to determine the serum level of Dickkopf-1 (Dkk-1) in peripheral blood of neonates with hypoxic ischemic encephalopathy (HIE). METHODS: We measured serum levels of Dkk-1 by ELISA in neonates with HIE (n = 20) within 24 h from symptom onset and in healthy controls (n = 20). RESULTS: Dkk-1 serum levels increased significantly in HIE neonates than in healthy control. DKK-1 serum levels increased significantly in HIE neonates with convulsion, using multiple anti-convulsant drugs and those complicated with cranial ultrasound changes. Serum DKK-1 levels increased significantly in severe HIE patients. CONCLUSION: Our study provides for the first time the evidence of releasing Dkk-1 into the circulation of neonates with HIE with higher level in severe degree.

Association of estrogen receptor ß and estrogen-related receptor α gene polymorphisms with bone mineral density in postmenopausal women.

The aim of the study was to investigate the possible association of AluI and RsaI polymorphisms of estrogen receptor ß (ER-ß) gene and 23-bp nucleotide repeat polymorphism of estrogen-related receptor α (ERRα) gene with bone mineral density (BMD) in postmenopausal Egyptian women. Two-hundred postmenopausal osteoporotic women as cases and 180 healthy age-matched postmenopausal women as controls were genotyped by PCR fragment length polymorphism for AluI, allele-specific PCR for RsaI, and by sizing of PCR products on agarose gels for ERRα repeats. sRANKL levels were estimated by ELISA. BMD measurements for spine and femoral neck were performed by dual energy X-ray absorptiometry. A significant difference between women with osteoporosis and controls regarding allele and genotype distributions of AluI G/A (OR 2.37, 95 % CI 1.77-3.18 and p < 0.001 for A allele) and ERRα polymorphisms (for the two repeats allele OR 2.08, 95 % CI 1.09-4.00, and p = 0.02). Osteoporotic women with the AluI AA + GA genotype or with the EERα 2,2 genotype had significantly lower BMD than did women with the other genotypes. Moreover, there was a significant increase of the mean values of sRANKL in carriers of AluI A, RsaI A alleles and in patients having 2,2 genotypes of ERRα (p < 0.001, p < 0.001, p = 0.02, respectively). We demonstrated an association of ER-ß AluI G/A and ERRα 23-repeats polymorphisms with BMD in postmenopausal Egyptian women. A possible effect of ER-ß and ERRα polymorphisms on the levels of sRANKL was estimated.

Genetic polymorphism of IL-23R influences susceptibility to HCV-related hepatocellular carcinoma.

BACKGROUND: Genetic variations may play an important role in the development of HCC in HCV patients. Variants of IL23R gene were investigated for association with many diseases like chronic inflammatory disorders, RA, inflammatory bowel diseases and the susceptibility to the development of gastric cancer but no data are available concerning the association of IL23R gene (rs11209026) polymorphism with HCC development in HCV patients. Therefore the current study aimed to analyze this polymorphism within the gene to evaluate its contribution to chronic HCV susceptibility and/or HCC development in Egyptian patients. SUBJECTS AND METHODS: One hundred and ninety-two patients with chronic HCV infection were included in this study (92 of them without HCC and 100 of them with HCC). One hundred healthy control subjects with no history of previous liver disease (HBV and HCV infection were negative) were included in the study. The IL23R polymorphism (rs11209026 G>A) were genotyped by real time PCR. RESULTS: We found a significant lower incidence of GA and AA genotype in HCV patients with HCC compared to those without HCC (p=0.026 and 0.040 respectively) and compared to control group (p=0.008 and 0.007 respectively). While, no significant difference between control and HCV patients without HCC groups was found. CONCLUSIONS: Our study suggests that wild type IL-23R GG serves as a risk factor for HCC and supports for the protective role of the rare variant rs11209026 (Arg381Gln) against HCV-related HCC in Egyptian patients.

Stool calprotectin in necrotizing enterocolitis.

BACKGROUND: Calprotectin is a 36 kDa protein present in the cytoplasm of the neutrophil has antimicrobial and apoptosis inducing activities. In vitro studies have shown that calprotectin inhibits the growth of various microorganisms. Necrotizing enterocolitis (NEC) remains one of the leading causes of morbidity and mortality in neonatal intensive care units (NICU), affecting up to 5% of premature infants. Fecal calprotectin is resistant to degradation and has been proposed as a useful marker of gastrointestinal inflammation. OBJECTIVE: The objective of the present study is to evaluate fecal calprotectin concentrations in NEC. STUDY DESIGN: Fifteen neonates with a clinical diagnosis of NEC were studied; they admitted at NICU of Zagazig University Hospital. In addition, 20 age sex matched neonates fed all caloric requirement served as the control group. All neonates were subjected to history taking, clinical examination, laboratory investigations (complete blood count, C-reactive protein) and determination of stool calprotectin. RESULTS: There was a highly significant increase in fecal calprotectin in patients than control and there was a highly significant increase in its fecal level in died patients than living one. Also significant increase in fecal calprotectin level with increasing severity of NEC. CONCLUSION: Fecal calprotectin measurements could be a valuable tool for the investigation of preterm and full term infants suspected of having NEC.