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Article
Toll-Like Receptor 4 Gene Polymorphisms in patients withUrinary Tract Infection

Authors: Hammadi A. Al-Hilaly --- AliN. Salman --- Ahmed H. Dakheel
Journal: Univesity of Thi-Qar Journal مجلة جامعة ذي قار العلمية ISSN: 66291818 Year: 2015 Volume: 10 Issue: 3 Pages: 1-12
Publisher: Thi-Qar University جامعة ذي قار

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Abstract

Background: Urinary tract infection (UTIs) are considered to be the most common infections in humans.Aims:The present study aimed to investigate the association between single nucleotide polymorphisms (SNPs) in the toll-like receptor 4 (Tlr4) gene (Thr399Ile) and the incidence of Urinary Tract Infection.Subjects and Methods:A total of 49 patients with Urinary Tract Infection and 25 apparently healthy control were enrolled in this study. Urine samples from patients with UTI was collected in AL-Imam AL-Hussain teaching hospital in Thi- Qar province, during the period from February 2014 to March 2015.. Urinary isolates were identified by conventional methods.DNA was extracted from the blood samples taken from these participants. TLR4 gene was amplified with polymerase chain reaction (PCR) using specific primers. Genotyping of the SNPs of interest was done by restriction fragment length polymorphism (RFLP).Results:The present study was showed 26 (53.06%)isolates Escherichia coli; 9 (18.37%) isolates had Pseudomonas aeruginusa;7 (14.29 %) isolates had Klebsiella pneumonia; 4 (8.16%) had Proteus and 3 (6.12%) isolates had Klebsiellaoxytoca, the results showed the presence of heterozygous in one sample from study group at site 399 (C / T) after using restriction enzyme Hinf1.Conclusion: Escherichia coli was most common causative agent in UTI, Thr399Ile may be considered as a risk factor that increases susceptibility to Urinary TractInfection


Article
ASSOCIATION BETWEEN ASN142ASP GENETIC POLYMORPHISM OF GSTO2 AND SUSCEPTIBILITY TO BLADDER CANCER

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Abstract

Background:The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in glutathione S-transferase Omega 1,2 (GSTO1, GSTO2), and GSTP1 genes have been related to risk for bladder cancer.Objective:To assess a comprehensive picture of the relationship between smoking and GSTO2 gene Asn142Asp variant (rs156697) with bladder cancerMethods:A case control study was conducted at Chemistry and Biochemistry Department, College of Medicine and DNA Research and Training Center, Al-Nahrain University from February 2014 to September 2014. Forty one bladder cancer patients and 41 age matched apparently healthy controls were participated in this study. Genotyping of the GSTO2 Asn142Asp polymorphism was evaluated using a polymerase chain reaction fragment length polymorphism (PCR-RFLP) method. The odds ratio (OR) and 95% confidence interval (CI) were calculated as a measure of the combined effect of cigarette smoking and the GSTO2 Asn142Asp polymorphism on bladder cancer risk.Result:It was found that subject with the GSTO2 Asp/Asp genotype have significantly increased bladder cancer risk (OR 4.92; 95% CI =1.32 - 18.30). A statistically highly significant increased the bladder cancer risk was also found in ever smoker of the GSTO2 (Asn/Asn) (OR =11.8; 95% CI=2.43 - 57.84) and (Asn/Asp +Asp/Asp) (OR =12.8; 95% CI=3.23 - 51.41) compared with never smoker Ala/Ala genotype.Conclusion:The study suggests that smokers having GSTO2 Asn/142Asp polymorphism could play an important role as risk factor for the development with bladder cancer.Keywords:Bladder cancer, single nucleotide polymorphism, glutathione S-transferase, GSTO2, Asn142Asp, smoking, rs156697.


Article
The Impact of Single Nucleotide Polymorphisms in the Gene of Toll-Like Receptor-4 in Prostate Cancer
تأثير التغييرات الجينية المنفردة في جين المستقبل الشبيه للتول 4 في سرطان البروستات

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Abstract

Background: Prostate cancer is one of the major medical problems in male population. Chronic inflammation has an important role in many human cancers and could be involved in the etiology of prostate cancer. Toll-like receptors are important tolls in innate immunity to pathogens. Many environmental factors could predispose for this cancer, however, genetic background of the population cannot be neglected. Objective: To explore the hypothesis that genetic variation in TLR4 gene can influence the individual's susceptibility to prostate cancer. Patients and Methods: A total of 95 outpatient men with histologically-proven prostate cancer as well as 45 apparently healthy men were recruited for this study. Blood samples were taken from each participant from which genomic DNA was extracted and TLR4 gene was PCR-amplified, using specific primers. PCR products were genotyped by direct sequencing.Results: Asp299gly and Thr399Ile SNPs had only two genotypes; the distributions of these genotypes were statistically not significant between prostate cancer patients and controls. At allele levels, the control group had significantly higher frequency in the mutant allele of Thr399Ile SNP (allele T) than prostate cancer patients. On the other hand, the rs11536889 had three genotypes with the mutant homozygous genotype (CC) and the mutant allele were more prevalent in PCa than controls with significant difference (OR=3.433, 95%CI=1.107-10.645, P= 0.033 and OR=2.730, 95%CI= 1.095-6.803, P=0.031 respectively). Conclusion: Allele T of Thr399Ile SNP may have a protective role, while allele C of rs11536889 SNP might increase the risk of prostate cancer.

خلفية الدراسة: يعد سرطان البروستات احد المشاكل الصحية لدى الذكور. الالتهاب المزمن يلعب دورا رئيسيا في العديد من السرطانات في البشر ومنها سرطان البروستات. المستقبلات الشبيهة للتول تلعب دورا هاما في المناعة ضد مسببات الامراض. عدد من العوامل البيئية لها تاثير مباشر في احداث السرطان بالاضافة الى العوامل الجينية. الهدف من الدراسة: ايجاد نظرية التغايرات الجينية في جينات مستقبل التول 4 الذي قد يؤتر في قابلية توليد سرطان البروستات لدى الرجال.المرضى وطرائق العمل: تم جمع 95 مريض مصاب بسرطان البروستات و 45 رجل غير مصاب بالمرض تم استخدامها كمجموعة سيطرة. تم سحب عينة دم من كل المشمولين بالدراسة واستخلاص الحامض النووي الرايبوزي (الدنا) من جميع العينات باستخدام تقنية تفاعل البلمرة للكشف عن جين مستقبل التول 4 بعدها تم تحديد انواع التغايرات الجينية لهذا المستقبل باستخدام السيكونسر المباشر (لتحديد تسلسل الجينات في هذا المستقبل)النتائج: اظهرت نتائج الدراسة انتشارا ذو دلالة غير احصائية في كل من الرضى والسيطرة بخصوص الجينان لمستقبل التول 4 (Asp299gly و Thr399Ile) وعلى مستوى المزدوجات فقد ظهر في مجموعة السيطرة نسبة عالية في التغاير الجيني اكثر مما في سرطان البروستات. (OR=3.433, 95%CI=1.107-10.645, P= 0.033 and OR=2.730, 95%CI= 1.095-6.803, P=0.031).الاستنتاج: بعض المزدوجات تظهر دورا حاميا ضد السرطان اما البعض الآخر يزيد نسبة الخطورة للاصابة بسرطان البروستات.

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