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.

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

BACKGROUND: Cytokines play an important role in the pathogenesis of acne vulgaris together with other genetic and environmental factors. OBJECTIVE: To check for the association of TNF-α and IL-10 gene polymorphisms with the susceptibility and severity of acne in Saudi patients. SUBJECTS AND METHODS: Study 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. RESULTS: Frequencies 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). CONCLUSIONS: TNF-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.

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

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.

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.

Association of cytokine gene polymorphisms with psoriasis in cases from the nile delta of egypt.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease with an immunogenetic background. This work was planned to check for the association of polymorphisms related to cytokine genes TNF-α(-308) (G/A), IL-10(-1082) (G/A), IL-6(-174) (G/C), and IL-1Ra (VNTR) with psoriasis in cases from Egypt. MATERIALS AND METHODS: This work included 46 cases with psoriasis recruited from the Dermatology Departments, University Hospitals, Nile Delta region of Egypt. They included 14 males and 32 females with an age mean ± SD of 46.68 ± 12.16 years and range of 15-70 years. Their genotypes were compared to 98 healthy controls of matched age and sex from the same locality. Genotyping was done through deoxyribonucleic acid amplification using PCR with sequence specific primers for polymorphic alleles. RESULTS: Compared to controls, cases showed significant higher frequency of certain genotypes including IL-6(-174) CC (P < 0.001, OR = 6.7), IL-10(-1082) GG (P < 0.05, OR = 5.1), and TNF-α(-308) GG (P < 0.05, OR = 3.7). TNF-α(-308) GG and IL-10(-1082) GG genotypes were higher among cases with plaque subtype of moderate severity. Combined heterozygosity for IL-10 GA, IL-6 GC with TNF GA showed a significant low frequency among studied cases. CONCLUSION: Genetic polymorphisms related to IL6, IL10, and TNF-α genes showed a particular pattern of association with psoriasis that may have a potential impact on disease counseling and management.

Cutaneous Manifestations of Hypothyroidism amongst Gynecological consultations.

OBJECTIVES: Many of the signs of hypothyroidism, affect the skin as well as the genital system of affected female cases. The aim of this study is to highlight the presenting dermatologic and gynecologic manifestations of firstly-diagnosed hypothyroid females. PATIENTS AND METHODS: This is a case control study that included 150 patients presenting for gynecological consultation. Out of them, 60 were affected with hypothyroidism and 90 were euthyroid based on clinical and laboratory investigation backgrounds. Their gynecologic and dermatologic findings were analyzed and compared statistically. RESULTS: Compared to euthyroid cases, hypothyroid ones were presenting mostly with amenorrhea (OR=7.76). Other gynecologic manifestations that were prominent in hypothyroid cases were dysparunia, PCO, PMS and Breast tenderness. On the other hand, rate of menstrual irregularities and infertility were non-significantly different in both groups. Hypothyroid women showed also significantly higher frequency of urticaria and puffiness of hands and feet (both were present in 16.7% in hypothyroid vs. 3.3% of euthyroid cases, p =0.007, OR=5.8). Hypothyroid cases showed also significantly higher frequency of yellow ivory skin (OR=5.4) and coarse rough dry skin (OR=3.8). On the other hand, alopecia and periorbital edema were observed only among cases of hypothyroidsm and none of euthyroid cases. CONCLUSION: A great index of suspicion should be always exerted to the diagnosis of disorders manifesting with subtle manifestations as hypothyroidism in female cases particularly having gynecologic and dermatologic disorders.

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.

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.