Red blood cell alloimmunization in blood transfusion-dependent ß thalassemia major patients in Sana'a City-Yemen.

The development of erythrocyte alloantibodies complicates transfusion therapy in ß thalassemia major patients. These antibodies increase the need for blood and intensify transfusion complications. Data on erythrocyte alloimmunization is scarce in Yemeni thalassemia patients. We studied the frequency of alloimmunization in multitransfused ß-thalassemia major patients and investigated risk factors that affect antibody formation. Blood samples were taken from 100 ß thalassemia major patients who received multitransfused leukodepleted packed red-blood cells. Antibody screening and identification were performed by indirect antiglobulin test using the gel column technique. All patients were tested for autoantibodies using autocontrol and direct antiglobulin test. No adsorption test was done as no autoantibodies were detected in any patient. In our study of 100 ß-thalassemia patients, 50 were male and 50 were female with ages ranging from 1 to 30 years. Alloantibodies were present in 6% of patients, while no autoantibodies were detected. Of the 17 alloantibodies identified, the majority were directed against Kell (41.2%) and Rh (29.4%) blood groups. Alloimmunization was significantly associated with age group and sex (p = 0.013, p = 0.030), respectively in ß thalassemia major patients. The development of alloantibodies was not significantly associated with duration, total number of transfusions and splenectomy (P = 0.445, P = 0.125, P = 0.647). No autoantibodies found in patients with ß thalassemia major. The study found low rates of erythrocyte alloimmunization in multitransfused ß-thalassemia major patients, but significant alloantibodies were produced primarily from Kell and Rh blood groups, suggesting the need for providing phenotypically matched cells for selective antigens to improve transfusion efficiency.

ABO, Lewis blood group systems and secretory status with H.pylori infection in yemeni dyspeptic patients: a cross- sectional study.

BACKGROUND: The ABO and Lewis blood group antigens are potential factors in susceptibility to H. pylori infection. This research aimed to examine the prevalence of Helicobater pylori (H.pylori) infection and its association with ABO, Lewis blood group systems, and secretory status in Yemeni symptomatic patients. METHODS: In a cross-sectional study, 103 patients referred for endoscopy due to dyspepsia were included. H pylori infection was assessed using stool antigen and serum antibody rapid tests. ABO and Lewis blood group systems were examined using hemagglutination assay. Saliva samples were investigated for identification of the secretory phenotype using hemagglutination inhibition test. RESULTS: The prevalence of H. pylori infection was (80.6%), with a higher rate of infection in females than males. The ABO blood groups were found to be significantly different between males and females (p = 0.047). The O blood group was prevalent among H. pylori patients, especially secretors. There was a significant association between ABO blood groups and H. pylori infection (p = 0.001). The Le (a + b+) phenotype was the most common, followed by Le (a + b-), Le (a-b+), and Le (a-b-). Lewis blood group systems and secretory status of symptomatic patients were not associated with H. pylori infection. The results showed that serum Ab test for H. pylori achieved poor sensitivity (68%), specificity of 55%; positive predictive value (PPV) 86%, negative predictive value (NPV) 29% and accuracy 65.1%. CONCLUSION: The prevalence of H. pylori infection was high in Yemeni patients. This infection was linked to the O and Le (a + b+) secretor phenotype. The H. pylori stool Ag test is the most reliable noninvasive diagnostic method for detecting H. pylori infection.

Plasma Lipocalin-2 and Adiponectin are Affected by Obesity Rather Than Type 2 Diabetes Mellitus per se.

PURPOSE: Changes in plasma adipocytokines and inflammatory markers in type 2 DM remain controversial as to whether they are due to obesity or directly associated with the diabetic state. Our objective was to study the effect of obesity and diabetes on plasma lipocalin-2 (LCN2), adiponectin, and interleukin-1ß (IL-1ß) by comparing their levels in non-diabetic obese subjects and non-obese type 2 DM patients, as well as determining the association of these adipocytokines with metabolic syndrome factors and diabetic parameters. PATIENTS AND METHODS: In this study, 85 Yemeni male volunteers aged 30-60 years old were enrolled, 25 of whom were healthy subjects with BMI < 25 kg/m2 served as control; 30 non-diabetic obese subjects (BMI ≥ 30 kg/m2 and FBG < 6.1 mmol/l); and 30 non-obese type 2 DM patients (BMI < 25 kg/m2 and FBG > 7 mmol/l). RESULTS: Lipocalin-2 and adiponectin were significantly (p = 0.043 and p = 0.034) lower in non-diabetic obese subjects by 16.2% and 29.7% with respect to control group, with no effect in the non-obese type 2 DM patients. Moreover, LCN2 was significantly (p = 0.04) lower in the non-diabetic obese subjects by 15.8% as compared with the non-obese type 2 DM patients, with no significant difference in adiponectin levels. In contrast, serum IL-1ß was significantly (p = 0.001 and p = 0.003) higher in both non-diabetic obese subjects and the non-obese type 2 DM patients by 76.5% and 67.7% as compared to control group. The significant decrease in both LCN2 and adiponectin and the significant increase in IL-1ß in the non-diabetic obese subjects disappeared upon adjustment for waist circumference (WC). In contrast, the significant increase in IL-1ß in the non-obese Type 2 DM patients was not affected upon adjustment for WC. CONCLUSION: Plasma LCN2 and adiponectin were not affected by diabetes per se, suggesting that the observed changes in LCN2 and adiponectin in type 2 DM may be due to obesity rather than the diabetic state, whereas IL-1ß levels were affected by both obesity and diabetes.

Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute Lymphoblastic Leukemia in a Yemeni Population.

BACKGROUND: Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent. METHODS: Seven single-nucleotide polymorphisms (SNPs) in IKZF1, three SNPs in DDC, two SNPs in CDKN2A, two SNPs in CEBPE, and three SNPs in LMO1 were genotyped in 289 Yemeni children (136 cases and 153 controls), using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Logistic regression analyses were used to estimate ALL risk, and the strength of association was expressed as odds ratios with 95% confidence intervals. RESULTS: We found that the IKZF1 SNP rs10235796 C allele (p = 0.002), the IKZF1 rs6964969 A>G polymorphism (p = 0.048, GG vs. AA), the CDKN2A rs3731246 G>C polymorphism (p = 0.047, GC+CC vs. GG), and the CDKN2A SNP rs3731246 C allele (p = 0.007) were significantly associated with ALL in Yemenis of Arab-Asian descent. In addition, a borderline association was found between IKZF1 rs4132601 T>G variant and ALL risk. No associations were found between the IKZF1 SNPs (rs11978267; rs7789635), DDC SNPs (rs3779084; rs880028; rs7809758), CDKN2A SNP (rs3731217), the CEBPE SNPs (rs2239633; rs12434881) and LMO1 SNPs (rs442264; rs3794012; rs4237770) with ALL in Yemeni children. CONCLUSION: The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.

Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was associated with protection against acute lymphoblastic leukemia. In conclusion, our study has shown that ARID5B variants are associated with acute lymphoblastic leukemia in Yemeni children with several gender biases of ARID5B single nucleotide polymorphisms reported.

Altered circulating concentrations of active glucagon-like peptide (GLP-1) and dipeptidyl peptidase 4 (DPP4) in obese subjects and their association with insulin resistance.

OBJECTIVES: Soluble DPP4 (sDPP4) is a novel adipokine that degrades glucagon-like peptide (GLP-1). We evaluated the fasting serum levels of active GLP-1 and sDPP4 in obese, overweight and normal weight subjects to assess the association between sDPP4 levels, active GLP-1 levels and insulin resistance in obese subjects. METHODS: The study involved 235 Malaysian subjects who were randomly selected (66 normal weight subjects, 97 overweight, 59 obese subjects, and 13 subjects who were underweight). Serum sDPP4 and active GLP-1 levels were examined by enzyme-linked immunosorbent assay (ELISA). Also, body mass index kg/m2 (BMI), lipid profiles, insulin and glucose levels were evaluated. Insulin resistance (IR) was estimated via the homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: Serum sDPP4 levels were significantly higher in obese subjects compared to normal weight subjects (p=0.034), whereas serum levels of active GLP-1 were lower (p=0.021). In obese subjects, sDPP4 levels correlated negatively with active GLP-1 levels (r2=-0.326, p=0.015). Furthermore, linear regression showed that sDPP4 levels were positively associated with insulin resistance (B=82.28, p=0.023) in obese subjects. CONCLUSION: Elevated serum sDPP4 levels and reduced GLP-1 levels were observed in obese subjects. In addition, sDPP4 levels correlated negatively with active GLP-1 levels but was positively associated with insulin resistance. This finding provides evidence that sDPP4 and GLP-1 may play an important role in the pathogenesis of obesity, suggesting that sDPP4 may be valuable as an early marker for the augmented risk of obesity and insulin resistance.

Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects.

BACKGROUND: Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV). METHOD: Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels. RESULTS: Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects. CONCLUSIONS: DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects.