Ahmad Settin

Methylenetetrahydrofolate Reductase Gene Polymorphisms in Egyptian Women with Unexplained Recurrent Pregnancy Loss

AIMSnThis work aims at testing for the association of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with unexplained recurrent pregnancy loss (RPL) among Egyptian women.nnnSUBJECTS AND METHODSnParticipants were 70 cases having a history of two or more events of unexplained RPL and 136 controls with a good obstetric history. Detection of MTHFR C677T and A1298C mutations was done by polymerase chain reaction with restriction fragment length polymorphisms assay using restriction enzymes HinfI and MboII respectively.nnnRESULTSnCompared with controls, cases with unexplained pregnancy loss showed higher frequency of the homozygous mutant MTHFR 677 TT, 1298 CC genotypes, and the mutant haplotype 677T/1298C, although not reaching statistical significance. The frequency of 677 mutant genotypes (TT or TC) combined with either the mutant 1298 (CC or AC) or normal 1298 (AA) genotypes was significantly increased among cases with late-stage pregnancy loss versus those with early-stage pregnancy loss (p=0.001). There was also increased frequency of the 677 mutant genotypes among cases with secondary infertility compared with those with primary infertility and among cases with pregnancy loss >4 times compared with those with ≤4 times but with no statistical significance. Regarding other risk factors, it was noted that the frequency of mutations among cases with no or just one risk factor did not differ significantly from those having two or more risk factors (p=0.98).nnnCONCLUSIONSnMutations related to the MTHFR gene are increased but not statistically significant in Egyptian women with unexplained pregnancy loss. Interaction with other genetic variants might be speculated and need to be investigated.

Tumor necrosis factor-α −308 G/A and interleukin 10 −1082 A/G gene polymorphisms in patients with acne vulgaris

BACKGROUNDnCytokines play an important role in the pathogenesis of acne vulgaris together with other genetic and environmental factors.nnnOBJECTIVEnTo check for the association of TNF-α and IL-10 gene polymorphisms with the susceptibility and severity of acne in Saudi patients.nnnSUBJECTS AND METHODSnStudy subjects included 166 Saudi patients (65 males, 101 females) with acne vulgaris. Their mean age±SD was 21.6±5.1 years. These cases were compared to 390 unrelated healthy controls (208 males, 182 females) with a mean age±SD of 20.1±3.3 years. Cases were sub-grouped on the basis of their severity of acne affection into mild, moderate and severe groups. For all participants, genotypic variants of the TNF-α -308 G/A and IL-10 -1082 A/G genes were determined using the real time PCR technique.nnnRESULTSnFrequencies of genotypic variants of the TNF-α -308 polymorphism were significantly different in acne cases compared to controls. Further analysis showed that acne cases had significantly higher frequency of both the GG and AA homozygous forms than controls (73.8% vs. 63.6%, p=0.02, odds ratio=1.6). It was also interestingly noticed that the amount of GG homozygosity was notably higher among female cases than male ones (76.0% vs. 54.7%, p=0.006, odds ratio=2.6) whereas male cases had a higher frequency of AA and GA genotypes than female ones (9.4% and 35.9% vs. 4% and 20% respectively). Differences in the frequencies of IL-10 -1082 genotypic variants were statistically insignificant comparing cases to controls (p=0.3). On the other hand, comparing cases-subgroups in terms of the age of onset of the disease, consanguinity, family history, obesity and acne severity; no statistical significance was observed regarding frequencies of genotypic variants related to the both TNF-α -308 and IL-10 -1082 polymorphisms (>0.05).nnnCONCLUSIONSnTNF-α -308 polymorphic variants might be a predisposing factor for acne susceptibility, with no apparent relation to its severity whereas IL-10 -1082 variants showed no association with both acne susceptibility and severity.

Association of MTHFR C677T and A1298C Gene Polymorphisms with Hypertension

OBJECTIVESnTo 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.nnnSUBJECTS AND METHODSnParticipants 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 polymorphismsnnnRESULTSnTotal 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).nnnCONCLUSIONnThis 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

BACKGROUNDnHypertension is a result of complex factors including multiple genetic polymorphisms.nnnOBJECTIVEnThis 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.nnnSUBJECTS AND METHODSnThis 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.nnnRESULTSnHypertensive 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).nnnCONCLUSIONnThis 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.

BACKGROUNDnMyocardial infarction (MI) can be due to inherited thrombophilia caused by resistance to activated protein C resulting from factor V Leiden (FVL) mutation.nnnOBJECTIVESnThe 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.nnnSUBJECTS AND METHODSnSubjects 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.nnnRESULTSnAlthough 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).nnnCONCLUSIONnThere 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.

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

BACKGROUNDnHypertension and cardiac diseases are multifactorial disorders with genetic background determined by multiple gene polymorphisms.nnnMETHODSnThis 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.nnnRESULTSnCarriers 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.nnnCONCLUSIONnThe 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.

Association of IL-4-590 C>T and IL-13-1112 C>T Gene Polymorphisms with the Susceptibility to Type 2 Diabetes Mellitus

Background. The goal of the study is to investigate the association of IL-4-590 and IL-13-1112 genetic polymorphisms with type 2 diabetes mellitus (T2DM) in Egyptian patients. Subjects and Methods. The study included 135 cases with T2DM and 75 healthy unrelated age-matched controls from the same locality of Egypt. DNA was extracted and processed by the ARMS-PCR technique for characterization of genetic variants of IL-4-590 C>T and IL-13-1112 C>T polymorphisms. Results. Egyptian cases with T2DM showed a lower frequency of the IL-4-590 CC homozygous genotype compared to controls (10.4% versus 43.48%) with a higher CT heterozygous genotype (85.2% versus 47.8%). Similarly, cases showed a lower frequency of the IL-13-1112 CC genotype (20.7% versus 56.8%) with a higher frequency of the heterozygous IL-13-1112 CT genotype (76.3% versus 41.3%). Both polymorphisms showed significantly positive associations with T2DM in the dominant, codominant, and overdominant models of inheritance. On the other hand, comparing genotypes of subgroups related to gender, positive family history, and positive consanguinity showed a nonsignificant difference (P > 0.05). Conclusion. Heterozygous genotypes (IL-4-590 CT and IL-13-1112 CT) could be considered as risk factors, while the homozygous wild types (-590 CC and -1112 CC) might be considered protective to T2DM.