Association of CYP2C9 Genetic Variants with Vitiligo

BACKGROUND: Vitiligo is a depigmenting skin disorder in which genetic factors play an important role. OBJECTIVE: To examine the association of CYP2C9 *1/*2/*3 gene polymorphism with vitiligo. METHODS: In this case controlled study, 95 Saudi patients with vitiligo (50 men and 45 women), with a mean age of 27.3 years, were analyzed. Patients were compared to 86 healthy controls from the same locality (76 men and 10 women), with a mean age of 20.1 years. In all participants, DNA was extracted and processed for characterization of 2C9 *1/*2/*3 gene variants using real time-polymerase chain reaction. RESULTS: Vitiligo patients have a significantly higher CYP2C9 *3 allele carriage rate compared to controls (32.7% versus 4.7%, p=0.00, odds ratio=9.9, 95% confidence interval=3.3~29.6). On the other hand, frequencies of CYP2C9 *2 genotypes and alleles did not show any significant difference between vitiligo cases and controls. When the frequencies of CYP2C9 genotypes were compared among subgroups of age, gender, family history, and disease patterns, the cases with positive consanguinity had significantly higher frequencies of homozygous genotypes than others (p=0.029). CONCLUSION: CYP2C9 *3 allele carriage is probably associated with vitiligo susceptibility.

Factors influencing parental consent for participation in clinical research involving their children in Egypt

Factors affecting parents' decision to involve their children in clinical research have not been studied in all cultural backgrounds. We aimed to explore the attitudes and beliefs influencing parents' decision to involve their children in clinical research in Mansoura, Egypt. Of 523 families approached, 357 filled the questionnaire. Only 98 [27.5%] parents consented to involve their child in clinical research. The children of consenters were significantly older than refusers: 8.6 [SD 7.2] versus 2.6 [SD 1.2] years. Factors favouring consent were: research of benefit to child [84.7%], enough explanation about the benefits [40.8%] and to learn more about child's condition [29.6%]. Factors favouring refusal were: use of new drugs or vaccines [89.6%] and invasive procedures [84.2%]. Parents' rate of consent was positively correlated with the research being non-invasive and the belief that research was of benefit to their child and negatively correlated with belief that refusal may negatively affect the care provided to their child

Polymorophisms in MTHF and ACE genes and the association with hypertension among Saudi population from Qassim region

Three clinically important mutations; Two of the methyl-tetrahydrofolate reductase [MTHFR] gene namely C677T, A1298C, and insertion/deletion [I/D] polymorphism of the angiotensin converting enzyme [ACE] gene are reported to be associated with various pathological conditions. This study is planned in order to evaluate the association of genetic polymorphisms related to these genes with hypertension. These polymorphisms can be utilized as biomarkers for susceptibility and severity of the disorder with a potential impact on diagnosis and management. Participants included 117 cases [78 males and 39 females] with an age mean +/- SD of 50.93 +/- 15.43 years. They were hospitalized for hypertensive complications including cardiac affection [64.9%] and renal dysfunction [17.9%] or strokes [20%]. For comparison, 169, age and sex matched; with an age mean +/- SD of 47.65 +/- 11.15 normal healthy unrelated subjects [78 males and 91 females] were taken from the same locality as controls. For all participants, DNA was extracted followed by real-time PCR amplifications for characterization of genotypes and alleles related to MTHFR C677T, A1298C and ACE I/D gene polymorphisms. Compared to controls, cases showed significantly higher frequency of the heterozygous genotypes of MTHFR AC [52.1% vs. 36.5%, p<0.05] and ACE ID [96.5% vs. 43.5%, p<0.0001]. Cases showed also significantly higher MTHFR 1298 mutant C allele carriage rate with nonsignificant higher carriage rate for the MTHFR 677 mutant T allele and ACE mutant D allele. It was also noted that 74% of cases carried at least one of the 3 studied mutant forms. Comparing case-subgroups in terms of being either positive or negative for diabetes, cardiac, renal or cerebral complications and obesity showed non-significant difference related to the studied genotypes and alleles. This work shows that genetic polymorphisms related to the methyltetrahydrofolate reductase [MTHFR] and angiotensin converting enzyme [ACE] genes are associated probably with other environmental factors as that imposed by smoking and obesity. With the risk of hypertension among Saudi subjects from Qassim region

Eosinophilic cationic protein: is it useful in assessing control of childhood asthma?

This study evaluated peripheral eosinophil and serum eosinophilic cationic protein [s-ECP] levels as markers of asthma control. A total of 38 children with asthma [16 controlled and 22 partially controlled] were compared with 16 age- and sex-matched healthy children. Total asthma cases had higher eosinophil counts and s-ECP levels than healthy children and partially controlled asthmatics had significantly higher levels of both markers than controlled asthmatics. Controlled asthma cases showed non-significant changes in both parameters versus healthy children. A negative correlation was noted between degree of asthma control and both eosinophil counts and s-ECP levels [r = -0.60 and -0.75 respectively]. s-ECP as well as peripheral eosinophil count may be helpful in the assessment of asthma control

Lymphocytes DNA content, p53, C-MYC and BCL-2 as predictive markers in childhood with acute lymphoblastic leukemia

Cell cycle parameters as well as apoptotic and tumor markers directly control cell growth. DNA ploidy and S phase fraction, apoptosis fraction in addition to apoptotic inducer [p53, c-myc] and antiapoptotic marker [Bcl-2] were investigated in childhood with acute lymphoblastic leukemia [ALL] leukemia as a predictive markers represented in survival data. This study included 70 children with [ALL]; 38 males and 32 females; of median age 5 years. Event free survival [EFS] and overall survival [OS] were estimated for all studied cases. Cell cycle and apoptotic parameters as well as p53, c-myc and Bcl-2 were analyzed using FACS caliber flow cytometer in the lymphocyte cells of peripheral blood. Aneuploidy constituted 33% of studied cases. The median overall survival [OS] showed higher significant values when S% was <4.5%, and DNA index was >/= 0.94 and p53 was < 70.87, whereas it showed no significant difference related to G0/G1%, G2/M% and aneuploidy%. The median event free survival [EFS] showed significant higher value at Bcl-2 >/= 81.5 but with no significance related to other cell cycle parameters as well as p53 and c-myc. These data suggest that DNA index, S phase fraction, p53 and BcI-2 may be useful as a predictive markers that help patients' stratification and adjusting protocols of ALL therapy

Association of cytokine gene polymorphism with susceptibility andd clinical types of leprosy

Both pro- and anti-inflammatory cytokines are implicated in development and prognosis of leprosy so the genetic regulation of such cytokines could play an important role. This study was planned for testing the association of cytokine gene polymorphisms with susceptibility and clinical types of leprosy among Egyptian cases. This study included 47 cases [29 men, 18 females, mean age = 46.3 years] with leprosy in addition to 98 healthy unrelated controls [52 males, 46 females, mean age = 44.9 years]. Cases were recruited from Leprosy Clinics, Delta region of Egypt. Cases were classified into paucibacillary [PB] [n=17; 10 males, 7 females; mean age 42.6 years] and multibacillary [MB] [n= 29; 19 males, 10 females; mean age 43.9 years]. For all cases and controls, DNA was extracted and amplified using polymerase chain reaction with sequence specific primers [PCR-SSP] for detection of single nucleotide polymorphisms [SNPs] in the promoter regions of cytokine genes, TNF - alpha - 308 [G/A], IL-10-1082[G/A], IL-6-174[G/C] as well as IL-1RaVNTR in intron 2 of the gene. Compared to controls, all cases have shown increased frequency of homozygous genotypes: IL-10-1082 [GG] [Odds ratio 6.6, P <0.05], homozygous TNF-alpha-308 [GG] [Odds ratio = 3.23], and homozygous IL-1Ra [11] [Odds ratio = 3.6, P<0.05] with increased frequency of IL10 G and ILRa 1 alleles [P<0.05] with increased frequency of IL10G allele [P<0.05]. On the other hand, MB subgroup showed increased frequency of homozygous TNF-alpha-308 [GG] [Odds ratio = 5.84, P<0.05]. and homozygous IL-1Ra [11] [Odds ratio= 4, P<0.05] with increased frequency of IL-1Ra 1 allele [P<0.05]. There is predominance for heterozygous IL-6-174 [G/C] polymorphism in all studies patient subgroups as well as controls with no significant difference among them. Genetic polymorphisms related to TNF-alpha-308 and IL-10-1082 and IL-1Ra may be used as genetic markers for susceptibility and clinical outcome of leprosy among Egyptian cases from the Nile Delta

Dose monitoring of health care workers occupationally exposed to ionizing radiation in Mansoura university hospitals

This study aims at evaluating the efficacy of radiation safety in Mansoura University Hospitals [MUHs] and to establish practical dose constraint [DC] for medical application. The study has been conducted upon health care workers [HCWs] occupationally exposed to ionizing radiation in various diagnostic and therapeutic activities in six health premises of MUHs. Four medical applications [radiotherapy, nuclear medicine, general radiology and interventional radiology] and five specialties [medical doctors, physicists, technicians, nurses and non-classified personals] were accounted. Doses were measured on a quarterly basis using thermoluniscent dosimeters [TLD-badges], while pocket dosimeters were used whenever TLD was not available. The annual doses were collected to build up a data base for years 1994-2005. The results show that TLD-badges were used in best situation in Oncology and Nuclear Medicine Dept. to cover less than one third of the exposed HCWs. The occupational doses showed a highly significant difference [p<0.0001] depending on the field of medical application. It is found that HCWs in radiotherapy were exposed to an average annual dose of 1.36 +/- 0.61mSv/y. For interventional radiology, the mean annual dose was found 2.25 +/- 2.47mSv/y unlike that of general radiology 1.07 +/- 0.65mSv/y. The largest sources of occupational exposure came from fluoroscopic radiology .equipments [1.76 +/- 0.92mS/y] followed by Cobalt-60 teletherapy machine [1.12 +/- 0.72mS/y]. The study showed that about 90% of HCWs received doses less than 2mSv/y and only 1.39% reported doses 5mSv or above. Dose constraint level can be set at 2mSv/y in premises of MUHs that may be considered achievable ceiling value referring to acceptably applied practices rather than optimized ones

Genetic analysis of rheumatic fever among Egyptian families: consanguinity pattern, segregation analysis and blood group association

To assess genetic background of Rheumatic Fever [RF] among Egyptian families and to test for association to blood group allelic phenotypes. This study was done on 30 Egyptian rheumatic families of which 10 were mutiplex; enrolled from Pediatric Cardiology Clinic, Mansoura University Hospital. Subjects included 30 probands and 1142 relatives of different degrees; they were classified clinically into 46 cases with RF, 136 subjects with recurrent Upper Respiratory Infection [URTI] and/or arthralgia and the remainders were irrelevant. Diagnosis of RF was based on Jones criteria. Pedigree analysis with stress on consanguinity, positive family history of RF and definite recurrent URTI. Nine blood group systems were analyzed for probands including; ABO, Rh, MNS, Kell, Lutheran, Lewis, Kidd, Duffy, P1 and individual secretor status. In rheumatic families consanguinity and inbreeding were higher than control [53.3%, 0.015]. Segregation analysis suggested multifactorial inheritance for RF with mean heritability [30%] whereas recurrent URTI followed recessive inheritance. Some alleles and phenotypes were of higher incidence in probands compared to control; alleles se [non-secretor], D, Jka+ and phenotypes Lu [a-b-], Le [a-b-] and Fy [a-b-] were of higher frequency, whereas alleles Se [secretor], A, B, Kp a+, Lu b+, Le b+, Fy a+, Fy b+ and phenotypes Fy [a+ b+], Sese or SeSe [secretor] were less frequent. Based on the inherited susceptibility to respiratory infection, RF is a genetic disease with multifactorial inheritance. Blood group systems on chromosome 19 could mark hot spots for further linkage and gene mapping

TNF-alpha [-308], IL-10 [-1082] and IL-1Ra [VNTR] gene polymorphism in leprosy cases from the Nile Delta region of Egypt

This study examined the genotype frequencies of three promoter polymorphic sites in the TNF-alpha, IL-10 and IL-genes as well as IL-1Ra VNTR in leprotic patients to investigate whether the genetic regulation of their production could be implicated in leprosy pathogenesis and prognosis. DNA from 47 leprotic patients and 42 healthy controls, all from Gharbia, Egypt, were examined with the polymerase chain reaction in a case-controlled study. The polymorphic sites in genes of the TNF-alpha at position -308, IL-10 at position -1082 and IL-6 at position -174 as well as 86-base pair variable number tandem repeat within intron 2 of the IL-1Ra gene were determined. It was speculated that there is a complex interaction between cytokine gene polymorphisms and phenotypic iversity of cells network that contribute to the host defense

Assessment of the role of blood group systems and three DNA loci [ALU TPA-25, Humfes / Fps and HuMf 13A1] in paternity testing in a sample of Egyptian population

A panel of 10 genetic markers has been applied for paternity testing in 51 Egyptian families. The panel included 7 blood group system [ABO, Rh, MNSs, Duffy, Lewis, Kell, and Kidd], and 3 DNA loci [Alu RPA - 25, HUMFES / FPS, and HUMF13A1]. The trio in each family consisted of the mother, the child, and the legal or alleged father. The families were studied as 3 groups of statistical significance: The 1st 40th family group in which paternity of legal fathers was tested despite the lack of any suspicion of paternity dispute [expected low probability of disputed paternity], the 41st - 51st family group in which paternity of legal fathers was tested due to strong suspicion paternity dispute [expected higher probability of disputed paternity], and the 1st - 51st family group in which paternity of 10 known foreign men [to represent alleged father with 100% true paternity dispute] was randomly tested in the 51 families of the study. The study included determination of blood groups by the agglutination method, and analysis of DNA loci by aggarose gel electrophoresis after DNA extraction and amplification by polymerase chain reation. Exclusion of paternity was concluded from the knowledge of modes of inheritance of the study markers, and probability of paternity [inclusion of paternity] was calculated from the studied gene freqencies after gene typing of the study population. Results of the study showed that the DNA loci were better than blood group systems in exclusion and inclusion of paternity, though both failed to exclude all the alleged fathers or to give reliable values of probability of paternity. The Lewis, Kell, and Kidd blood groups were nearly of no value in paternity testing whereas the polymorphic DNA loci [HUMFES / FPS and HUMF13A1] provided the best result. Some true disputed fathers were excluded by single markers only, raising the importance of such exclusion which should be considered seriously and cautiously and cautiously. Its reliabilityy should be scrutinized, abd it may be necessary to examine more markers. It has been concluded that the study panel of 10 genetic markers was not adequate in excluding or proving paternity for all test cases, and that the polymorphic markers provide better results in paternity testing. In a certain population, paternity testing should rely upon adequate number of the most valuable genetic markers, and regulatory rules regarding reliable paternity exclusion or inclusion or inclusion parameters are mandatory, as well as strict application of quality control parameters to the concerned laboratories

Biochemical study of anxiety among secondary school adolescents

This work was carried out on 376 adolescent students of the first and second grades of secondary schools in Mansoura District. They were chosen through a stratified cluster sample. Anxiety score was done according to the standardized Arabic translation of Taylor's Test. Relevant data to anxiety were fulfilled through a structured questionnaire. 41.5% of these 376 students were sampled. The results revealed that, male adolescents with severe anxiety had significantly higher levels of total cholesterol [TC] and low density lipoprotein cholesterol [LDL-C] and significant decrease of high density lipoprotein [HDL-C]. Regarding corresponding lipoprotein values in female adolescents, there were no significant differences in different anxiety scores. From the questionnaire, 33.5% and 41.8% of adolescent pupils were suffering from severe and mild to moderate anxiety. Also, urban residence, lower socioeconomic standard of the family and absence of friends all are important factors contributing to anxiety state. So, mental and physical health care is recommended for this neglected age group as well as education and guidance programs are advisable

Normal lipoprotein profile of adolescent students

We planned this work to establish the arbitrary normal values of total cholesterol [TC], low density lipoprotein [LDL-C], high density lipoprotein - cholesterol [HDL-C], and triglycerides [TG] among school adolescents, [aged 14 - 21 years] in Mansoura district, 341 normal adolescent students were enrolled in the study through a related questionare including their socio-demographic data.Out of them 201 were sampled for laboratory studies after their constant. The mean values of TC, LDL-C, HDL-C and TG in males were 155.4, 85.8, 51.3 and 79.6 mg/dl respectively. Their 5th to 95th percentiles were [108.2-219.5], [38.1-138.0], [36.0-70.9] and [32.5-161.7] mg-dl respectively. In females, the corresponding mean values were [123.3-233.8], [57.6-187.2], [32.073.8] and [40.3-134.2] mg/dl respectively. Our levels were compared with the western levels. There were no significant difference regarding variations of these parameters related to their sex, residence, social class or smoking.We hope such data to be of benefit in the determination of the preliminary cut -off values at which the risk of coronary artery disease [CAD] is increased. This will be clearly of help for the ultimate purpose of preventing such disorder later on in life