Moataz Dowaidar

Frequency of factor V Leiden mutation in Egyptian cases with myocardial infarction

Abstract Background: Acute myocardial infarction (MI) is death or necrosis of myocardial cells due to lack of blood supply. One of the causes may be thrombosis resulting from inherited resistance to activated protein C caused by the factor V Leiden (FVL) mutation. Objectives: To check for the presence of FVL mutation among Egyptian cases with MI compared to normal population controls. Subjects and methods: This study is a form of a prospective controlled study including 44 MI cases with an age ranging from 25 to 80 years and sex of 36 males (81·8%) and 8 females (18·2%). These cases were taken randomly from those admitted in the Intensive Care Units of Mansoura University Hospitals, Egypt. Of these cases, 10 cases (55·6%) were smokers, 7 cases (75·0%) had a positive family history of MI, 8 cases (18·18%) were diabetic and 20 cases (45·45%) were hyperlipidemic. For association and risk analysis, cases were compared to 211 healthy unrelated control subjects of matched age and sex. Factor V Leiden (G1691A) gene mutation was detected using a multiplex allele-specific PCR amplification. Results: Mutant A allele frequency of factor V Leiden was significantly higher in cases (30·68%) than in controls (10·19%) (p<0.0001, OR=3·9). Total cases showed significant higher frequency heterozygous mutant genotype GA (43·0%) compared to controls (16·6%), (p<0.0001, OR=4·45). Also total cases showed significant higher frequency of the homozygous mutant genotype AA (9·0%) compared to controls (1·9%), (p=0.0094, OR=8·19). On the other hand, no significant difference was found between cases subgroups related to age, sex, smoking, diabetes and hyperlipedemia. Conclusion: Frequency of factor V Leiden mutation among Egyptian cases with myocardial infarction is relatively high. So, families of affected subjects should be genotyped and counseled for proper prophylaxis.

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.

Prevalence of α-1-Antitrypsin gene mutations in Saudi Arabia

Background/Aim: α-1 antitrypsin (AAT) deficiency results from mutations of the protease inhibitor (PI). The AAT gene is mapped on chromosome 14 and has been associated with chronic liver disease and chronic obstructive pulmonary disease (COPD). Objective: To determine the frequency of AAT mutations on S and Z carrier alleles in healthy Saudi individuals from Qassim Province in Saudi Arabia. Patients and Methods: A total of 158 healthy, unrelated participants from Qassim Province were recruited. They were genotyped for the two AAT-deficiency alleles, PI*S and PI*Z, using polymerase chain reaction, with primers designed throughout to mediate site-directed mutagenesis. Results: Of the 158 subjects, 11.39% were carriers for the S mutation (i.e., had the MS genotype), whereas 2.53% were carriers for the Z mutation (i.e., had the MZ genotype). The SZ genotype was present in 3.8% of subjects, while the homozygous genotype SS was present in 1.9% of subjects. No subjects showed the ZZ mutant genotype. Accordingly, frequency of the mutant S and Z alleles of AAT gene was 9.49% and 3.19%, respectively. Conclusion: The results obtained showed a high prevalence of the AAT deficiency allele in the Saudi population. This probably warrants adoption of a screening program for at-risk individuals, so that they might initiate adequate prophylactic measures.

Risk of myocardial infarction related to factor V Leiden mutation: a meta-analysis.

BACKGROUND Myocardial infarction (MI) can be due to inherited thrombophilia caused by resistance to activated protein C resulting from factor V Leiden (FVL) mutation. OBJECTIVES The objectives of this study were to estimate the frequency of FVL mutation among MI cases in various populations and calculate the overall risk related to it. SUBJECTS AND METHODS Subjects comprised 7790 cases with MI and 19,276 healthy controls collected from 41 relevant studies in the search databases. The resulting frequency of FVL mutation among cases and the odds ratio were compared and integrated in a meta-analysis format. RESULTS Although there was marked variation of the frequency of FVL mutation among different populations including MI and healthy controls, most studies reported a positive risk related to it. Compilation of analyzed studies resulted in an overall frequency of FVL mutation of 6.791% among MI cases, which was significantly higher than that among controls (1.304%, p = 0.0) with an overall odds ratio of 1.608 (95% confidence interval, 1.98-4.44). CONCLUSION There is a definite risk related to the carriage of FVL mutation among MI cases. This should have a potential impact on the genetic counseling of family members of affected cases for proper prophylaxis.

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.