Gastroenterology manifestations and COVID-19 outcomes: A meta-analysis of 25,252 cohorts among the first and second waves.

A meta-analysis was performed to identify patients with coronavirus disease 2019 (COVID-19) presenting with gastrointestinal (GI) symptoms during the first and second pandemic waves and investigate their association with the disease outcomes. A systematic search in PubMed, Scopus, Web of Science, ScienceDirect, and EMBASE was performed up to July 25, 2020. The pooled prevalence of the GI presentations was estimated using the random-effects model. Pairwise comparison for the outcomes was performed according to the GI manifestations' presentation and the pandemic wave of infection. Data were reported as relative risk (RR), or odds ratio and 95% confidence interval. Of 125 articles with 25,252 patients, 20.3% presented with GI manifestations. Anorexia (19.9%), dysgeusia/ageusia (15.4%), diarrhea (13.2%), nausea (10.3%), and hematemesis (9.1%) were the most common. About 26.7% had confirmed positive fecal RNA, with persistent viral shedding for an average time of 19.2 days before being negative. Patients presenting with GI symptoms on admission showed a higher risk of complications, including acute respiratory distress syndrome (RR = 8.16), acute cardiac injury (RR = 5.36), and acute kidney injury (RR = 5.52), intensive care unit (ICU) admission (RR = 2.56), and mortality (RR = 2.01). Although not reach significant levels, subgroup-analysis revealed that affected cohorts in the first wave had a higher risk of being hospitalized, ventilated, ICU admitted, and expired. This meta-analysis suggests an association between GI symptoms in COVID-19 patients and unfavorable outcomes. The analysis also showed improved overall outcomes for COVID-19 patients during the second wave compared to the first wave of the outbreak.

Evaluation of vitamin D receptor gene polymorphisms (Fok-I and Bsm-I) in T1DM Saudi children.

BACKGROUND: Vitamin D deficiency conferred strongest susceptibility to pathogenesis of type 1 diabetes mellitus (T1DM). Altered gene expression and function have strong effect on VDR gene polymorphism. OBJECTIVES: We aimed to check for the association of two single nucleotide polymorphisms (SNPs) in VDR gene (Fok-I and Bsm-I) with T1DM in Saudi children. SUBJECTS AND METHODS: Cross-sectional study included 100 T1DM Saudi children, plus 102 unrelated healthy subjects. PCR technique was used for detection of Fok-I and Bsm-I SNPs in VDR gene. RESULTS: Regarding the Fok-I polymorphisms, T1DM cases showed a significant increased frequency of the heterozygous genotype (Ff) than controls (33% vs 21%, OR = 1.9, 95% CI = 1.006-3.587, P = .04). In the meantime, they showed significantly lower frequency of the homozygous (ff) genotype (64% vs 79%, OR = 0.51, 95% CI = 0.28-0.96, P = .03). Cases showed also a significantly lower frequency of the (f) allele than controls (80.5% vs 87.7%, OR = 0.57, 95% CI = 0.33-0.995, P = .04). On the other hand, cases showed significantly higher frequency of the Bsm-I homozygous (bb) and heterozygous (Bb) genotypes (25% vs 11.8%, P = .01, OR = 2.5, 95% CI = 1.18-5.31) & (45% vs 27.5%, P = .0, OR = 2.1, 95 % CI = 1.20-3.89, respectively). Cases showed also significantly higher frequency of (b) allele compared to control (47.5% vs 25.5%, P = .0, OR = 2.6, 95% CI = 1.74-4.02). Haplotype analysis showed an increased risk with the fB and fb haplotypes. CONCLUSION: This study emphasizes a positive association between SNPs (Fok-I and Bsm-I) and T1DM among Saudi children with increased risk with the Fok-I F and Bsm-I b alleles.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) +1858 C>T gene polymorphism in Egyptian cases with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The gene encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been reported to be associated with RA in several populations. OBJECTIVES: This work aimed at assessing the association of PTPN22 +1858 C>T gene polymorphism with the susceptibility, activity and severity of RA in Egyptian subjects. SUBJECTS AND METHODS: This study included 112 unrelated RA patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for PTPN22 +1858 C>T (rs2476601) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cases showed significantly higher PTPN22 +1858 T allele carriage rate (CT+TT genotypes) compared to controls (34.8% vs. 8.2%, OR=5.98, 95% CI=2.81-12.73, p<0.001). Also the frequency of the PTPN22 +1858 T allele was significantly higher among cases compared to controls (18.7% vs. 4.5%, OR=4.89; 95% CI=2.45-9.76, p<0.001). Cases positive to the PTPN22 T allele (CT+TT genotypes) showed no significant difference from those with the CC genotype regarding clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p=0.04). CONCLUSIONS: This study is a confirmatory evidence of the association of the PTPN22 +1858 T allele with susceptibility and functional disability of RA in Egyptian subjects.

Fat mass and obesity-associated (FTO) and leptin receptor (LEPR) gene polymorphisms in Egyptian obese subjects.

BACKGROUND: Several studies addressed the contribution of fat mass and obesity-associated (FTO) and leptin receptor (LEPR) polymorphisms for the susceptibility to obesity among different ethnic subjects. The main purpose of this work is to evaluate the association of these polymorph\isms with obesity among Egyptian subjects. SUBJECTS AND METHODS: This case-control study was carried out on 110 unrelated obese Egyptian subjects who were compared with 122 controls. Their genomic DNA was genotyped using the PCR technique. RESULTS: The allelic frequencies of FTO rs9939609 (A) and LEPR rs1137101 (223R) were significantly higher in obese subjects compared with non-obese controls (p < .001). Comparing different phenotype frequencies including clinical, anthropometric, and biochemical parameters in obese subjects revealed no significant difference in relation to their genotype frequencies (p> .05). CONCLUSIONS: This study designates a strong association for FTO and LEPR variants with the risk of obesity among Egyptian subjects.

Angiotensin-converting enzyme gene insertion/deletion polymorphism in Egyptian patients with myocardial infarction.

INTRODUCTION: This work aimed to test the association of the angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism with myocardial infarction. SUBJECTS AND METHODS: This study comprised 79 Egyptian myocardial infarction cases with a mean age of 54.4+/-9.9 years including 60 males and 19 females, plus 238 healthy unrelated individuals of nearly matched age and sex as a control group. For all subjects, DNA testing for the angiotensin-converting enzyme gene I/D polymorphism was done using PCR amplification for detection of both the D and I alleles followed by a second run PCR specific for the I allele for samples typed as DD in the first run. RESULTS: Cases had a higher frequency of DD (29.1%) and ID (62.0%) genotypes than II (8.9%) genotype, with a higher frequency of D allele than I allele (64.4% vs. 33.6%). Compared to controls, cases had a significantly higher frequency of ID genotype (62.0% vs. 47.5%, p<0.05).This was more apparent among cases in the low risk group (p=0.002) than in the high risk group (p=0.041). CONCLUSION: The angiotensin-converting enzyme gene I/D polymorphism is probably a risk factor for ischaemic heart disease among Egyptian cases, particularly if integrated with other environmental and genetic risk factors.

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 study was planned to check for the association of polymorphisms related to cytokine genes TNF-alpha-308(G/A), IL-10-1082(G/A), IL-6-174(G/C), and IL-1Ra (VNTR) with psoriasis in cases from Egypt. METHODS: This study included 46 cases with psoriasis recruited from the Department of Dermatology, University Hospitals, Nile Delta region of Egypt. They included 14 males and 32 females with a mean age +/- SD of 46.68 +/- 12.16 years and a range of 15 to 70 years. Their genotypes were compared to 98 healthy controls of matched age and sex from the same locality. Genotyping was done through DNA amplification using PCR with sequence-specific primers for polymorphic alleles. RESULTS: Compared to controls, cases showed a significantly 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-alpha-308 GG (p < 0.05, OR = 3.7). Combined heterozygosity for IL-10 GA, IL-6 GC, and TNF GA showed a significant low frequency among the cases studied. CONCLUSION: Genetic polymorphisms related to the IL6, IL10, and TNF-alpha genes showed a particular pattern of association with psoriasis that may have a potential impact on disease counseling and management.

The effectiveness of alitretinoin for the treatment of chronic hand eczema: A meta-analysis.

Alitretinoin is a new oral retinoid authorized for use in grownups that have severe chronic hand eczema (CHE). A comprehensive search to solicit all studies of alitretinoin for the treatment of CHE. A comprehensive search to solicit all studies of alitretinoin for the treatment of CHE including randomized controlled trials (RCTs) or uncontrolled trials, re-treatment studies, open-label studies, or observational studies, along with case series of 10 or more participants. Physician global assessment (PGA), patient global assessment (PaGA) and modified total lesion symptom score (mTLSS) are the methods and outcomes criteria. Generated effect size and 95% confidence intervals were calculated for the outcomes. Heterogeneity and publication bias were also tested for all selected trials. When a noteworthy Q statistic (P < 0.1) demonstrates the heterogeneity crosswise over studies, an arbitrary impact model is used. On the other hand, a settled effect model is when heterogeneity is not shown. The initial search yielded 408 records of which 15 articles were selected. The 15 clinical trials included 3734 patients with CHE. Among alitretinoin-treated patients, the PGA effect size was directly proportional to the drug dosage, ranging from 40% to 69%, while the PaGA score ranged from 28.8% to 62.4%, and mTLSS ranged from 60.4% to 76.9%, much higher than placebo. A higher drug dose was about twice as effective as lower dose. The odds ratio for a better outcome with drug treatment taking duration into account was about 3-4 times that versus placebo. In conclusions, alitretinoin cleared lesions in about 50% of cases, particularly using a higher dose for a longer duration.

Genetic polymorphisms of IL-23R (rs7517847) and LEP (rs7799039) among Egyptian patients with hepatocellular carcinoma.

BACKGROUND: Genetic polymorphisms of IL-23 R (rs7517847) and LEP (rs7799039) have been stated to be associated with various types of human cancers. The purpose of this work is to test the association of these genetic polymorphisms with hepatocellular carcinoma (HCC) among Egyptian patients. SUBJECTS AND METHODS: This study involved 150 unrelated Egyptian HCC patients in addition to 100 healthy controls from the same locality. DNA was genotyped for these genetic polymorphisms using the PCR-RFLP technique. RESULTS: The frequency of the IL-23 R (rs7517847) G and LEP (rs7799039) G alleles were significantly higher among HCC patients compared to controls (p = .004 and .02). However, HCC patients with the IL-23 R GG and LEP GG genotypes showed no significant difference compared to others regarding their clinical and laboratory markers. CONCLUSIONS: IL-23 R (rs7517847) and LEP (rs7799039) polymorphisms were associated with an increased risk but not affecting the clinical presentation of HCC among Egyptian patients.

Genetic polymorphisms of NFκB1-94ins/delATTG and NFκBIA-881A/G genes in Egyptian patients with colorectal cancer.

To assess the association of genetic polymorphisms of NFκB1 and NFκBIA genes with the susceptibility to colorectal cancer (CRC). Subjects included 100 Egyptian patients with CRC (60 males and 40 females) in addition to 85 healthy controls (47 males and 38 females) from the same locality. For all participants, genetic polymorphisms of NFκB1-94ins/delATTG (rs28362491) and NFκBIA-881A/G (rs3138053) were detected by using restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). CRC patients showed a significantly higher frequency of the NFκB1-94ins/ins genotype than controls (30 vs. 4.7%) that was significant in the recessive (OR 17.69, 95% CI 5.41-57.82, p < 0.0001) and codominant models (OR 18.28, 95% CI 4.87-68.6, p < 0.0001). The NFκB1-94ins allele frequency was significantly higher among patients than controls (58 vs. 39%, OR 2.18, 95% CI 1.4-3.3, p = 0.0004). We also noticed that the genotype G/G of NFκBIA-881 polymorphism was present in patients (4%) while it was absent (0%) in controls with increased frequency of the NFκBIA-881G allele in patients compared to controls (23 vs. 14%, p = 0.041). These polymorphisms were more associated with smoking and advanced tumor staging. This study indicates that the NFκB1-94ins/ins genotype was associated with the risk of developing colorectal cancer in Egyptian subjects. Also, CRC cases showed an increase in the frequency of NFκBIA-881G allele but not reaching statistical significance for multiple comparisons.

African vs. Caucasian and Asian difference for the association of interleukin-10 promotor polymorphisms with type 2 diabetes mellitus (a meta-analysis study).

BACKGROUND: Interleukin-10 (IL-10) is a multifunctional regulatory cytokine that might be associated with increased risk of type 2 diabetes mellitus (T2DM). IL-10 gene polymorphisms have been reported to be associated with T2DM in several ethnic populations with controversial results. OBJECTIVES: This work is an updated meta-analysis aiming at the evaluation of the association between IL-10 gene polymorphisms: rs1800872 (- 592 C > A), rs1800896 (- 1082 A > G) and rs1800871 (- 819 C > T) with the risk of T2DM. METHODS: All available full text studies published up to July 2015 were included in this meta-analysis. Mainly Pubmed and Science Direct databases were searched for all eligible studies pertinent to testing the association between IL-10 gene polymorphisms with the susceptibility to T2DM. Further analyses of the pooled and stratified data in terms of individual polymorphic types and subject ethnicity were done and assessed using varied genetic models. RESULTS: Fifteen case-control studies with a total of 26 comparisons (10 for IL-10 - 592 C > A rs1800872, 11 for IL-10 - 1082 A > G rs1800896 and 5 for IL-10 - 819 C > T rs1800871 polymorphisms) met our inclusion criteria. IL-10 - 1082 A > G polymorphism was the only one to show an association with T2DM in all pooled sample particularly among Asian and European (high frequency of the G allele) ethnic groups. On the other hand, IL-10 - 592 C > A and - 819 C > T were significantly associated with T2DM only among African subjects. CONCLUSIONS: This meta-analysis demonstrated that IL-10 - 1082 A > G polymorphism was associated with increased risk of development of T2DM in total subjects no matter was their ethnic background, while both IL-10 - 592 C > A and - 819 C > T polymorphisms were associated with that risk only among African subjects.

Association of PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with rheumatoid arthritis: A meta-analysis update.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The genes encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) and signal transducer and activator of transcription 4 (STAT4) have been reported to be associated with RA in several ethnic populations. OBJECTIVES: This work aims to assess the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility through an updated meta-analysis of available case-control studies. METHODS: A literature search of all relevant studies published from January 2007 up to December 2014 was conducted using Pubmed and Science Direct databases. The observed studies that were related to an association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility were identified. Meta-analysis of the pooled and stratified data was done and assessed using varied genetic models. RESULTS: Thirty-seven case-control studies with a total of 47 comparisons (29 for PTPN22 rs2476601 polymorphism and 18 for STAT4 rs7574865 polymorphism) met our inclusion criteria. The meta-analysis showed an association between PTPN22 T allele, CT+TT and TT genotypes with RA susceptibility. Furthermore, The meta-analysis showed an association between STAT4 T allele, GT+TT and TT genotypes with RA susceptibility. Stratification of RA patients according to ethnic groups showed that PTPN22 T allele, CT+TT genotypes, STAT4 T allele and STAT4 GT+TT were significantly associated with RA in European, Asian, African subjects, while PTPN22 TT genotype was significantly associated with RA in European but not in Asian and African subjects and STAT4 TT genotype was significantly associated with RA in European and Asian but not in African subject. A subgroup analysis according to the presence or absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with RA susceptibility may not be dependent on RF and anti-CCP antibodies. CONCLUSIONS: Our meta-analysis demonstrated that PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms confers susceptibility to RA in total subjects and in major ethnic groups. The association may not be dependent on RF and anti-CCP antibodies.

Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) +49 A>G gene polymorphism in Egyptian cases with rheumatoid arthritis.

BACKGROUND: The gene encoding cytotoxic T lymphocyte associated antigen-4 (CTLA-4) has been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The aim of this work is to assess the association of this polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. SUBJECTS AND METHODS: This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy controls from the same locality. For all subjects, DNA was genotyped for CTLA-4 +49 A>G (rs231775) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The frequency of the CTLA-4 G allele was significantly higher among cases compared to controls (37.1% vs. 23.4%, OR=1.93; 95% CI=1.29-2.89, p=0.002). Also, the frequency of CTLA-4 +49 G allele carriage (AG+GG genotypes) was significantly higher among cases with RA compared to controls (61.6% vs. 41.8%, OR=2.23, 95% CI=1.32-3.77, p=0.003). Logistic regression analysis showed that cases positive to the G allele (GA+GG genotypes) had less frequency of rheumatoid deformities and also a lower DAS28-CRP score, yet with a higher visual analogue scale (VAS) i.e. more functional disability than other cases. CONCLUSIONS: CTLA-4 +49 G allele carriage was associated with increased susceptibility and functional disability of RA in Egyptian patients.

Leptin gene tetranucleotide repeat polymorphism in obese individuals in Egypt.

BACKGROUND: Leptin is a peptide hormone secreted by the adipose tissue. Genetic mutations of the leptin gene were reported to cause severe obesity. OBJECTIVES: This study was undertaken to investigate the association of the polymorphic tetranucleotide repeat locus 3' UTR of leptin gene with obesity in Egyptian cases. SUBJECTS AND METHODS: This study has included 120 subjects affected with obesity 57 of them were consistent with the diagnosis of metabolic syndrome (MS) while the rest (63) had simple obesity. These cases were compared to 83 normal weight healthy controls. All participants were subjected to an estimation of their body mass index (BMI), waist hip ratio (WHR), serum as well as characterization of leptin gene tetranucleotide repeat (TTTC)n polymorphism by PCR technique. RESULTS: Thirteen different alleles were identified in all cases of obesity versus only 5 alleles in normal controls. The most frequent allele was the 154 bp allele (57.5% in all cases of obesity vs. 92.2% in controls). Total cases with obesity showed a significantly higher carriage rate of class II alleles (I/II + II/II genotypes) compared to healthy controls (48.3% vs. 6.0%, OR=14.6, 95% CI=5.5-38.6, p=<0.0001). This was more apparent in the group with simple obesity (52.3% vs. 6.0%, OR=17.2, 95% CI=6.1-48.1, p=<0.0001) than in MS cases (43.9 % vs. 6.0 %, OR =12.19, 95% CI=4.9-30.4, p=< 0.0001). Interestingly, cases with MS did not differ from those with simple obesity regarding their class I or II allele frequencies (p> 0.05). Although serum lipids were significantly higher in obese cases compared to controls, no difference was found among obese cases with different leptin gene class genotypes (p> 0.05). CONCLUSIONS: Tetranucleotide repeat (TTTC)n polymorphism in the 3' UTR of the human leptin gene was associated with obesity in Egyptian obese cases showing higher class II allele carriage rate. However, the lipoprotein levels were not affected by this polymorphism.

Association of ACE and MTHFR genetic polymorphisms with type 2 diabetes mellitus: Susceptibility and complications.

HYPOTHESIS/INTRODUCTION: Polymorphisms of angiotensin converting enzyme (ACE) and methylene-tetrahydrofolate reductase (MTHFR) genes have been proposed to be associated with type 2 diabetes mellitus (T2DM) with conflicting results. This work was planned in order to check for the association of these polymorphisms with the susceptibility for and complications of T2DM among Egyptian cases. MATERIALS AND METHODS: This is a case controlled study involving 203 patients with T2DM and 311 healthy controls. Polymorphic variants of ACE I>D and MTHFR (677 C>T and 1298 A>C) were determined using the polymerase chain reaction (PCR) restriction analysis technique. RESULTS: The susceptibility to T2DM was higher among subjects having the MTHFR 677TT (odds ratio (OR)=2.2, p=0.01), MTHFR 1298 AA (OR=1.84, p=0.001) and ACE (ID+II) (OR=2.0, p=0.0007) genotypes. Logistic regression analysis showed that MTHFR 677T allele was a risk factor for diabetic retinopathy (DR) (OR=3.47, p<0.001), diabetic polyneuropathy (DPN) (OR=5.2, p<0.0001) and ischemic heart disease (IHD) (OR=2.9, p<0.05), while MTHFR 1298 C allele was a risk factor for DR (OR=4.2, p<0.001) and the ACE DD genotype was a risk factor for DPN (OR=3.1, p<0.001). CONCLUSIONS: The MTHFR 677 TT genotype was associated with T2DM susceptibility and complications (DR, DPN and IHD). The MTHFR 1298 CC, AC and ACE DD genotypes were associated with DR and DPN.

Interleukin-4 -590 T>C and interleukin-4 receptor Q551R A>G gene polymorphisms in Saudi cases with alopecia areata.

OBJECTIVES: Immunogenetic factors are known to play a role in the pathogenesis of alopecia areata (AA). This study aimed at investigating the association between AA with the polymorphisms of interleukin-4 (IL-4) promoter and receptor (IL-4R) genes. PATIENTS AND METHODS: This work is a case-control study that was conducted on 76 AA patients from Qassim region, Saudi Arabia. Patients were compared with 93 normal healthy controls from the same locality. Genomic DNA was extracted and processed using real-time PCR amplification for characterization of IL-4 -590 T>C and IL-4R Q551R A>G gene polymorphisms. RESULTS: Cases of AA showed a higher frequency of the IL-4 -590 CC homozygous genotype compared with controls (63.2 vs. 53.8%, P>0.05) with a lower frequency of the TT genotype (5.3 vs. 10.8%); yet, both were statistically nonsignificant (P>0.05). Regarding the IL-4R Q551R A>G polymorphism, cases and controls showed nearly equal frequencies of all variants, that is, with no significant difference. Although the frequency of the IL-4 C and the IL-4R A alleles was higher among cases than among controls (78.9 vs. 71.5% and 78.8 vs. 72.6%, respectively), this was also statistically nonsignificant (P>0.05). Comparing case subgroups in terms of their age of onset, sex, disease severity, consanguinity, and family history showed no statistically significant difference regarding the studied genetic variant. CONCLUSION: IL-4 -590 and IL-4R Q551R gene polymorphisms are not associated with the susceptibility and the clinical pattern of AA in Saudi patients. We recommend further research studies involving the estimation of cytokines both in the serum and in the local skin lesions or in cultured skin cells to figure out whether Th1 or Th2 pathways play a specific role in the pathogenesis of AA.

Signal transducer and activator of transcription 4 (STAT4) G>T gene polymorphism in Egyptian cases with rheumatoid arthritis.

BACKGROUND: The gene encoding signal transducer and activator of transcription 4 (STAT4) has been reported to be associated with rheumatoid arthritis (RA) in several populations. This work aimed at assessing the association of STAT4 G>T gene polymorphism with the susceptibility, activity and functional disability of RA in Egyptian subjects. SUBJECTS AND METHODS: This study included 112 unrelated RA Egyptian patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for STAT4 G>T (rs7574865) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Cases showed a significantly higher frequency of the STAT4 T allele carriage (GT+TT genotypes) compared to controls (51.8% vs. 31.1%, OR = 2.37, 95% CI = 1.39-4.05, p = 0.001). Also the frequency of the STAT4 T allele was significantly higher among cases compared to controls (30.4% vs. 16.8%, OR = 2.16, 95% CI = 1.39-3.35, p = 0.001). Cases positive to the STAT4 T allele (GT+TT genotypes) showed no significant difference compared to those with the GG genotype regarding their clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p = 0.02). CONCLUSIONS: This study gives an extra evidence to the association of the STAT4 T allele with the susceptibility and functional disability of RA.

Cure rate of Helicobacter pylori infection in Egyptian children related to CYP2C19 gene polymorphism.

OBJECTIVES: This study was done in order to investigate the effect of CYP2C19 genetic polymorphism on the cure rate of children who received proton pump inhibitors (PPI)-based triple therapy for treating Helicobacter pylori (H. pylori) infection. METHODS: Participants included 100 children with H. pylori-positive gastritis diagnosed by endoscopy and biopsy in addition to H. pylori stool antigen test. Cure rate was assessed after 1 month of completion of a triple treatment course for 14 days. CYP2C19 polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Results showed that cases with a CYP2C19 genotypic status consistent with the heterozygote extensive metabolizers (HetEMs) had a higher cure rate of H. pylori when compared with the homozygote extensive metabolizers (HomEMs) although it was statistically nonsignificant (84.6 vs. 69.2). In addition, the poor metabolizers (PMs) had a higher cure rate compared with those of the HomEMs which was also statistically nonsignificant (77.8 vs. 69.2). The cure rate was also higher among both the groups of HetEMs and PMs combined together compared to the HomEMs (OR = 2.15, p > 0.05). Comparing cases regarding their age, gender, and severity of H. pylori gastritis revealed a better cure rate in the age group >10 years, in females and in mild and moderate cases than other cases although statistically nonsignificant. CONCLUSION: The higher cure rate of H. pylori infection using the triple therapy for 2 weeks among HetEMs and PMs cases compared to the HomEMs might warrant a need for a therapy augmentation or modification for the HomEMs.

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.

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.

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.