Hisham Ismail

Association of MTHFR C677T and A1298C Gene Polymorphisms with Hypertension

OBJECTIVES To check for the association of genetic polymorphisms related to the methylenetetrahydrofolate reductase (MTHFR) gene namely C677T and A1298C with hypertension in Saudi affected subjects from Qassim region. SUBJECTS AND METHODS Participants included 123 Saudi hypertensive cases (83 males and 40 females) in addition to 250 (142 males and 108 females) unrelated healthy controls from the same locality. Their age mean ±SD was 50.93 ± 15.43 years. For all subjects, DNA was extracted followed by real-time PCR amplifications for characterization of genotypes and alleles related to MTHFR C677T and A1298C gene polymorphisms RESULTS Total cases showed significantly higher carriage rate for the mutant allele 677T compared to controls (40.7% vs. 26%, OR=1.9, 95% CI= 1.2-3.1) with a lower frequency of the wild type 677CC genotype (59.3% vs. 74%, p=0.004). The same was observed among cases-subgroups of hypertension associated with obesity with a notably higher odds ratio (OR=2.6, 95% CI=1.3-5.01, p=0.004). Total cases showed also significantly higher frequency of mutant 1298 C allele carriage rate compared to controls (59.3% vs. 42.4%, OR=1.98, 95% CI= 1.3-3.1) with a lower frequency of the normal AA genotype (40.7% vs. 57.6%, p=0.003). The same was observed among cases-subgroups of hypertension associated with both diabetes and obesity and among cases of hypertension with obesity, also with higher odds ratio (OR=2.6 and 2.2 respectively). CONCLUSION This work showed that genetic polymorphisms related to the MTHFR gene are associated with the risk of hypertension particularly when accompanied with obesity and diabetes among Saudi subjects.

CYP2J2 −50 G/T and ADRB2 G46A Gene Polymorphisms in Saudi Subjects with Hypertension

BACKGROUND Hypertension is a result of complex factors including multiple genetic polymorphisms. OBJECTIVE This study aims to check for the association of genetic polymorphisms of the cytochrome P450 2J2 (CYP 2J2) and beta-2-adrenergic receptor (ADRB2) genes with hypertension among Saudi subjects. SUBJECTS AND METHODS This study included 116 cases with documented hypertension of at least 1 year duration. Their data were compared to that of 250 unrelated healthy nonhypertensive subjects from the same locality. For all participants, DNA was extracted and analyzed using real time polymerase chain reaction technique for the identification of genotypic and allelic variants of the CYP2J2 -50 G/T and ADRB2 G46A genes. RESULTS Hypertensive cases showed a significantly higher frequency of mutant CYP2J2 -50 T allele carriage (TT and GT genotypes) compared with controls (odds ratio [OR]=3.7, p=0.0003). The same was observed among subgroups of hypertension associated with diabetes and obesity (OR=3.6, p=0.007) and cases with isolated hypertension (OR=8.4, p=0.0002). On the other hand, hypertensive cases, whether being isolated or associated with obesity and/or diabetes, showed a nonsignificant difference from controls in relation to all genotypic variants related to the ADRB2 G46A polymorphism (p>0.05). CONCLUSION This study showed positive association of CYP2J2 gene polymorphism with hypertension among Saudi cases.

Methylene Tetrahydrofolate Reductase and Angiotensin Converting Enzyme Gene Polymorphisms Related to Overweight/Obesity among Saudi Subjects from Qassim Region

Background: This work was planned to check for the association of polymorphisms related to methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE) genes with overweight/obesity among Saudi subjects from Qassim region. Methods: This work included 130 subjects having overweight or obesity and 111 normal controls. Their age mean ± SD was 27 ± 9.8 and 24 ± 8.8 years respectively. Their DNA was analyzed for polymorphisms of MTHFR; 677C/T and 1298 A/C and ACE; I/D genes using real-time PCR. Results: Genotype and allele frequencies of studied polymorphisms in cases of overweight/obesity showed no significant statistical difference compared to that of controls. However, on analysis of body mass index (BMI), cases showed slightly higher but statistically nonsignificant mean ± SD values among those carrying the mutant MTHFR 677 T allele (CT + TT vs. CC, 30.7 ± 4.5 vs. 29.9 ± 4.9), 1298 C allele (AC + CC vs. AA, 29.9 ± 4.1 vs. 29.7 ± 5.5) and ACE D allele (ID + DD vs. II, 30.0 ± 5.1 vs. 29.1 ± 2.8). In addition controls having the DD and ID genotypes showed higher statistically significant values of BMI than those of the II genotype (22.0 ± 1.9, 21.7 ± 2.6 and 19.5 ± 2.3 respectively, p < 0.05). Conclusion: There is no solid association of polymorphisms related to MTHFR and ACE genes with non-complicated overweight or obesity among Saudi subjects from Qassim Region.

ACE I/D and eNOS E298D gene polymorphisms in Saudi subjects with hypertension

Background: Hypertension has a multifactorial background based on genetic and environmental interactive factors. Objectives: We aimed to test for the association of the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) gene polymorphisms with hypertension. Subjects and methods: Participants included 120 Saudi patients with hypertension and 250 normal healthy controls. For all participants, DNA was processed for characterization of ACE I/D and eNOS E298D gene polymorphisms. Results: Hypertensive cases showed a significantly higher frequency of the ACE mutant D allele carriage (98.3% vs. 92.4%, p = 0.028, OR = 4.8). Cases with hypertension associated with diabetes and obesity showed 100% mutant D allele carriage. Regarding the eNOS E298D polymorphism, the frequency of the mutant D allele carriage was only observed to be higher among cases with hypertension associated with diabetes and obesity, in comparison with controls, yet not reaching statistical significance (41.2% vs. 34%, p > 0.05). Conclusions: There is increased frequency of ACE and eNOS mutant allele carriage among Saudi patients affected with hypertension, particularly if accompanied by obesity and diabetes.

Occult hepatitis B virus infection in Egyptian hemodialysis patients with or without hepatitis C virus infection

correspondence: nahed Ismail Department of Pathology and Department of Microbiology and Immunology, Meharry Medical college, 1005 Dr D. B. Todd Blvd, nashville, Tn, UsA Tel +1 615 327 6364 Fax +1 615 327 6409 email nismail@mmc.edu Abstract: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are frequent in patients with end-stage renal disease who are on maintenance hemodialysis. There are limited data about the prevalence of occult HBV infection in patients on long-term hemodialysis. Occult HBV is defined as positive HBV DNA in the blood in the absence of hepatitis B surface antigen in the serum. In this study, we determined the prevalence of occult HBV in hemodialysis patients with or without HCV infection. The study included 116 patients with end-stage renal disease on chronic hemodialysis, of whom 64 patients were HCV RNA positive (Group 1), and 52 were HCV RNA negative (Group 2). We found that four of 64 (6.3%) hemodialysis patients with HCV infection (Group 1) had occult HBV, while only two of 52 (3.8%) hemodialysis patients without HCV (Group 2) had occult HBV. We then examined whether gender-matched hemodialysis patients with positive HBV DNA in the two hemodialysis groups differed in specific parameters, ie, age, degree of liver dysfunction, and presence of coinfection with schistosomiasis, a common parasitic infection of the liver. We found no significant difference between the groups having positive HBV DNA with regard to serum levels of liver enzymes, aspartate transaminase, albumin, and hepatitis B core antigen (P . 0.05). However, we detected significantly higher levels of alanine transaminase, a prolonged duration of hemodialysis, and higher levels of schistosomal antibodies in Group 1 than in Group 2. Interestingly, we found that the presence of schistosomal antibodies, history of past blood transfusion, and longer hemodialysis duration could distinguish patients with occult HBV infection from those with HBV DNA negative infection in hemodialysis patients. In conclusion, the prevalence of occult HBV in chronic hemodialysis patients is low, and does not significantly differ between hemodialysis patients with or without HCV coinfection.

Methylenetetrahydrofolate Reductase and Angiotensin-Converting Enzyme Gene Polymorphisms Among Saudi Population from Qassim Region

BACKGROUND Hypertension and cardiac diseases are multifactorial disorders with genetic background determined by multiple gene polymorphisms. METHODS This work included 273 healthy unrelated subjects ethnically belonging to the Qassim region. Their age ranged from 18 to 60 years, with a median age of 20 years. They included 152 (55.7%) men and 121 (44.3%) women. Their DNAs were analyzed for genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR; 677C/T and 1298 A/C) as well as angiotensin-converting enzyme genes (ACE; insertion/deletion [I/D]) using real-time polymerase chain reaction. RESULTS Carriers of the mutant MTHFR 677 T allele (CT + TT) and that of the 1298 C allele (CC + AC) constituted 33.7% and 48.9% of studied subjects, respectively, whereas carriers of ACE gene mutant D allele (DD + ID) represented 93.3% of subjects. The allele frequencies of MTHFR 677T, 1298C, and ACE D alleles were 18.7%, 29.45%, and 72.5%, respectively. Haplotype analysis of characterized chromosomes revealed that 2.5% were likely to carry the three mutant alleles together, 30.91% were likely to carry two of the three mutant alleles, and 51.92% were likely to carry one mutant allele. CONCLUSION The Saudi population from the Qassim region is a carrier of a relatively large number of genetic alleles predisposing them to hypertension and cardiac diseases. This gives a warning to local health authorities for adoption of competent programs for prevention as well as early diagnosis and management.

The impact of environmental and agricultural pollutants on the prevalence of allergic diseases in people from Qassim, KSA

BACKGROUND There are multiple environmental factors that influence a sensitized (IgE antibody positive) patients predisposition to manifest allergic symptoms following allergen exposure. The majority of allergens are known to induce morbidity with chronic symptoms such as rhinitis, pruritis, dermatitis and urticaria. AIM To study the impact of environmental and agricultural pollutants with different pollens on the immunological, hematological and biochemical markers and to determine the prevalence of sensitization to allergens among exposed individuals as well as to identify the eliciting allergens. SUBJECTS AND METHODS Ninety six highly exposed individuals to environmental and agricultural pollution in addition to 20 as controls were selected. A solid phase enzyme-linked immunosorbent assay and the EUROLINE test kit were used for the quantitative determination of total IgE concentration and semi-quantitative in vitro assay of human IgE antibodies to some of the inhalant, ingestant and contactant allergens in serum samples, respectively. Percentage and absolute eosinophil counts and biochemical parameters were analyzed. RESULTS Thirteen (13.5%) out of the 96 studied highly exposed subjects were manifesting allergic symptoms. Higher significant total serum IgE levels and absolute eosinophil counts in groups 1 and 3 of the highly exposed individuals compared to the control group were found (p1=0.00, p3=0.001 and p1=0.016, p3=0.028, respectively). Higher sensitization with inhalant Timothy grass, Aspergillus fumigatus, Der. Farinae and Olive; ingestant Egg yolk, Mango, Strawberry and Codfish and with contactant Latex/plastic and Crude oil was found in the studied groups compared with the controls. CONCLUSION The present data suggest that the highly exposed subjects to pollution are at high risk of developing an allergy. For the screening of those with suspected allergen sensitization, the determination of specific IgE antibodies is a suitable marker of type I allergy.

Genetic polymorphisms of NFκB1 -94 del/ins ATTG, NFκB1A 2758 A>G and SUMO rs237025 G>A in psoriasis.

BACKGROUND Nuclear factor-κB (NF-κB) and small ubiquitin-like modifier (SUMO4) are key transcription factors involved in the regulation of immune responses and apoptosis. The aim of this study is to test for the association of NF-κB and SUMO gene polymorphisms with the susceptibility and severity of psoriasis among Saudi cases. SUBJECTS AND METHODS This is a case controlled study including 85 Saudi psoriasis patients in addition to 92 matched healthy unrelated controls from the same locality. For all participants, DNA was analyzed by PCR for characterization of NF-κB1 -94 del/ins ATTG, NF-κB IA 2758 A>G and SUMO rs237025 G>A gene polymorphisms. RESULTS Compared to controls, psoriasis patients showed a non-significant difference for all frequencies of genotypes and alleles of NF-κB1 ins/del, NF-κB1A A>G and SUMO4 G>A polymorphisms (p>0.05). However, cases with the plaque type had significantly higher frequency of the SUMO4 A allele carriage (GA+AA genoytpes) than the guttate type (78.6% vs. 21.4%, p=0.02). The PASI score was also significantly higher among cases with the NF-κB1A AA genotype than other cases (p=0.00). CONCLUSION Genetic polymorphisms of NF-κB1-94 ins/del ATTG, NF-κB IA 2758 A>G and SUMO4 rs237025 G>A were not associated with the susceptibility to psoriasis vulgaris in Saudi patients. However, it might be associated with the expressivity of the disease in terms of its clinical type and severity.

Frequency of thrombophilic genetic polymorphisms among Saudi subjects compared with other populations

Abstract Thrombophilic mutations increase the tendency toward thromboembolic disease. The aim of this study was to estimate the prevalence of the genetic variants related to thrombophilia among Saudis compared with other populations. Real-time polymerase chain reaction (PCR) genotyping was carried out to determine the polymorphic variants of factor V Leiden 1695G/A, prothrombin 20210G/A, plasmin activator inhibitor 1 4G/5G, methylene tetrahydrofolate reductase (MTHFR) 677C/T, MTHFR 1298A/C, and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) among a representative sample of healthy Saudi subjects. Carraige rate for each of the mutant variants of factor V Leiden (FVL) and FII genes constituted 2% of the surveyed subjects giving an allele frequency of 0.01, homozygous forms of plasminogen activator inhibitor-1 (PAI-1) gene 4G/4G, MTHFR 677TT, 1298CC, and ACE DD were present among 7.7, 2.55, 7, and 51.8% of subjects with a mutant allele frequency of 0.4, 0.19, 0.29, and 0.73, respectively. This study showed that the Saudi population has a peculiar pattern regarding thrombophilic mutations that might warrant additional considerations for prophylaxis.

Relationship Between Blood Lead Level and Elevated Blood Pressure in Hypertensive Patients: Implication of Nitric Oxide

The correlation between the blood lead (B-Pb ) levels and the values of blood pressure in hypertensive patients was investigated. Moreover, plasma levels of nitric oxide (NO), total antioxidants (TAOX) and malondialdehyde (MDA) were detected to investigate the correlations between the measured parameters and B-Pb levels in hypertensive patients. Fifty-five hypertensive patients were compared with fifty-three age and sex matched control group. The B-Pb levels were detected by flame atomic absorption spectrometry. The plasma levels of NO, TAOX and MDA were measured by colorimetric methods. In the hypertensive patients, B-Pb levels were significantly higher than controls. Concomitantly, the plasma levels of MDA were significantly increased while the plasma levels of NO and TAOX were significantly reduced in the hypertensive patients in comparison with controls. There were significant positive correlations between B-Pb and each of MDA, systolic and diastolic blood pressure. Conversely, a significant negative correlation was found between B- Pb and NO. Our study indicated that B-Pb level was associated with elevated blood pressure as well as oxidative stress in hypertensive patients. Moreover, the negative correlation between the B-Pb level and NO level may clarify their implication in cardiovascular disease and hypertension.