Riyadh Saif-Ali

Genetic diversity of Plasmodium falciparum isolates from Pahang, Malaysia based on MSP-1 and MSP-2 genes

BackgroundMalaria is still a public health problem in Malaysia especially in the interior parts of Peninsular Malaysia and the states of Sabah and Sarawak (East Malaysia). This is the first study on the genetic diversity and genotype multiplicity of Plasmodium falciparum in Malaysia.MethodsSeventy-five P. falciparum isolates were genotyped by using nested-PCR of MSP-1 (block 2) and MSP-2 (block 3).ResultsMSP-1 and MSP-2 allelic families were identified in 65 blood samples. RO33 was the predominant MSP-1 allelic family identified in 80.0% (52/65) of the samples while K1 family had the least frequency. Of the MSP-2 allelic families, 3D7 showed higher frequency (76.0%) compared to FC27 (20.0%). The multiplicity of P. falciparum infection (MOI) was 1.37 and 1.20 for MSP-1 and MSP-2, respectively. A total of seven alleles were detected; of which three MSP-1 allelic families (RO33, MAD20 and K1) were monomorphic in terms of size while MSP-2 alleles were polymorphic (two 3D7 and two FC27). Heterozygosity (HE) was 0.57 and 0.55 for MSP-1 and MSP-2, respectively.ConclusionsThe study showed that the MOI of P. falciparum is low, reflected the low intensity of malaria transmission in Pahang, Malaysia; RO33 and 3D7 were the most predominant circulating allelic families. The findings showed that P. falciparum has low allelic diversity with a high frequency of alleles. As a result, antimalarial drug efficacy trials based on MSP genotyping should be carefully interpreted.

Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in Malaysian subjects

BackgroundIncreased plasma plasminogen activator inhibitor-1 (PAI-1) activity and decreased tissue plasminogen activator (tPA) activity could be considered a true component of the metabolic syndrome (MetS) associated with an increased risk of developing cardiovascular diseases (CVD) and fibrinolytic abnormalities. The aim of this study was to investigate the association of tPA and its inhibitor PAI-1 with type 2 diabetes (T2D) and MetS and interrelationship between PAI-1and tPA activities and antigens in Malaysian T2D and normal subjects.MethodsThe plasma activities and antigens of PAI-1 and tPA and the levels of the tPA/PAI-1 complex as well as serum insulin, parameter of the coronary risk panel and plasma glucose at fasting state were studied in 303 T2D subjects (227 with MetS and 76 without MetS), 131 normal non-diabetic non-metabolic subjects and 101 non-diabetic MetS subjects.ResultsThe PAI-1 activity was higher in subjects with T2D with MetS (P = 9.8 × 10-19) and non-diabetic subjects with MetS (P = 3.0 × 10-15), whereas the tPA activity was lower in T2D with MetS (P = 0.003) as compare to normal subjects. Plasma tPA antigen levels were higher in subjects with T2D with MetS (P = 8.9 × 10-24), T2D without MetS (P = 1.3 × 10-13) and non-diabetic MetS subjects (P = 0.002). The activity and antigen of PAI-1 in normal subjects were related to insulin resistance (P = 2.2 × 10-4; 0.007). Additionally, the PAI-1 activity was associated with an increased waist circumference (P = 2.2 × 10-4) and decreased HDL-c (P = 0.005), whereas the tPA activity was associated with decreased FBG (P = 0.028). The highest correlation was between PAI-1 activity and its antigen (R2 = 0.695, P = 1.1 × 10-36) in diabetic subjects. The tPA activity negatively correlated with its antigen (R2 = -0.444, P = 7.7 × 10-13) in normal subjects and with the PAI-1 activity and antigen (R2 = -0.319, P = 9.9 × 10-12; R2 = -0.228, P = 3.4 × 10-6) in diabetic subjects.ConclusionsPAI-1 and tPA activities and antigens were associated with diabetes and MetS parameters in Malaysian subjects.

KCNQ1 haplotypes associate with type 2 diabetes in Malaysian Chinese Subjects.

The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) and haplotypes of potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) with type 2 diabetes (T2D) in Malaysian Chinese subjects. The KCNQ1 SNPs rs2237892, rs2283228 and rs2237895 were genotyped in 300 T2D patients and 230 control subjects without diabetes and metabolic syndrome. Two logistic regression models of analysis were applied, the first adjusted for age and gender while the second adjusted for age, gender and body mass index. The additive genetic analysis showed that adjusting for body mass index (BMI) even strengthened association of rs2237892, rs2283228 and rs2237895 with T2D (OR = 2.0, P = 5.1 × 10−5; OR = 1.9, P = 5.2 × 10−5; OR = 1.9, P = 7.8 × 10−5, respectively). The haplotype TCA containing the allele of rs2237892 (T), rs2283228 (C) and rs2237895 (A) was highly protective against T2D (Second model; OR = 0.17, P = 3.7 × 10−11). The KCNQ1 rs2237892 (TT), and the protective haplotype (TCA) were associated with higher beta-cell function (HOMA-B) in normal subjects (P = 0.0002; 0.014, respectively). This study found that KCNQ1 SNPs was associated with T2D susceptibility in Malaysian Chinese subjects. In addition, certain KCNQ1 haplotypes were strongly associated with T2D.

Evaluation of Chemopreventive Effects of Acanthus ilicifolius against Azoxymethane-Induced Aberrant Crypt Foci in the Rat Colon.

Background Acanthus ilicifolius, a mangrove medicinal plant, is traditionally used to treat a variety of diseases. The aim of this research is to assess the chemoprotective outcomes of A. ilicifolius ethanolic extract against azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in rats. Methodology/Principal Findings In our study, rats were arranged in to five groups. Rats in the normal control group were given subcutaneous injections of normal saline once weekly for 2 weeks. The AOM control, reference and treatment groups were given subcutaneous injection of AOM, 15 mg/kg body weight, once weekly for 2 weeks each. The reference group was treated with 35 mg/kg 5-Fluorouracil via intraperitoneal injection once weekly for 8 weeks, and the treatment groups were administered by gavage with 250 and 500 mg/kg A. ilicifolius extract daily for 8 weeks. Both normal and AOM control groups received the vehicle; 10% Tween-20 only. Rats treated with 250 mg/kg and 500 mg/kg of A. ilicifolius extracts showed a decrease in the mean number of ACF by 65% and 53%, respectively. Those fed with A. ilicifolius showed significantly decreased multiplicity of ACF formations when compared with the results from the AOM control group. The 250 mg/kg A. ilicifolius treatment group showed significant decreases in lipid peroxidation MDA levels when compared with the AOM control group. In immunohistochemistry staining, the proliferating nuclear cell antigen (PCNA)-positive cells were significantly higher in the AOM control group than in the A. ilicifolius-treated groups. RT-PCR showed that A. ilicifolius caused a change in the regulation of apoptosis-related genes expression. Conclusion/Significance The results of the current study show that AOM-treated rats receiving oral exposure to A. ilicifolius demonstrated a significant decrease in the number of ACF in the colon when compared to AOM-treated rats receiving vehicle only. A ilicifolius may be an effective herbal approach for the prevention of AOM-induced ACF in the rat colon.

Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters in Malaysian subjects

The plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat insertion/deletion polymorphisms might be genetic determinations of increased or decreased of their plasma activities. The aim of this study was to investigate the association of plasminogen activator inhibitor-1 4G/5G and tissue plasminogen activator Alu-repeat I/D polymorphisms with metabolic syndrome parameters in normal Malaysian subjects and to assess the impact of these polymorphisms on their plasma activities and antigens. The genetic polymorphisms were genotyped in 130 normal subjects. In addition, the plasma activities and antigens of plasminogen activator inhibitor-1 and tissue plasminogen activator as well as levels of insulin, glucose, and lipid profile at fasting state were investigated. The subjects with homozygous 4G/4G showed association with an increased triglyceride (p = 0.007), body mass index (p = 0.01) and diastolic blood pressure (p = 0.03). In addition, the plasminogen activator inhibitor-1 4G/5G polymorphism modulates plasma plasminogen activator inhibitor-1 activity and antigen and tissue plasminogen activator activity (p = 0.002, 0.014, 0.003) respectively. These results showed that, the plasminogen activator inhibitor-1 4G/5G polymorphism is associated with metabolic syndrome parameters, plasminogen activator inhibitor-1 and tissue plasminogen activator activities in Malaysian subjects, and may serve to increase the risk of type 2 diabetes and cardiovascular disease in Malaysian subjects.

Effect of Plasminogen Activator Inhibitor-1 and Tissue Plasminogen Activator Polymorphisms on Susceptibility to Type 2 Diabetes in Malaysian Subjects

Elevated activity of plasminogen activator inhibitor-1 (PAI-1) and decreased tissue plasminogen activator (tPA) activity are considered to be important risk factors for type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). The aim of this study was to investigate the association of the PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms with T2DM in Malaysian subjects. Serum insulin, coronary risk panel, plasma glucose, and PAI-1 4G/5G and tPA Alu-repeat I/D polymorphisms were studied in 303 T2DM subjects (227 with MetS and 76 without MetS) and 131 normal subjects without diabetes and MetS. Statistical analysis showed that the dominant and additive models of PAI-1 4G/5G polymorphism showed a weak association with T2DM without MetS (OR = 2.35, P = 0.045; OR = 1.67, P = 0.058). On the other hand, the recessive model of the tPA Alu-repeat I/D polymorphism showed an association with T2DM with MetS (OR = 3.32, P = 0.013) whereas the dominant and additive models of the tPA Alu-repeat I/D polymorphism were not associated with T2DM either with or without MetS.

IGF2BP2 alternative variants associated with glutamic acid decarboxylase antibodies negative diabetes in Malaysian subjects

Background The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects. Methods/Principal Findings IGF2BP2; rs6777038, rs16860234 and rs7651090 single nucleotide polymorphisms (SNPs) were genotyped in 1107 GADA negative diabetic patients and 620 control subjects of Asian from Malaysia. The additive genetic model adjusted for age, race, gender and BMI showed that alternative variants; rs6777038, rs16860234 and rs7651090 of IGF2BP2 associated with GADA negative diabetes (OR = 1.21; 1.36; 1.35, P = 0.03; 0.0004; 0.0002, respectively). In addition, the CCG haplotype and diplotype CCG-TCG increased the risk of diabetes (OR = 1.51, P = 0.01; OR = 2.36, P = 0.009, respectively). Conclusions/Significance IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject.

Impact of Metabolic Syndrome Factors on Testosterone and SHBG in Type 2 Diabetes Mellitus and Metabolic Syndrome

Objective Several studies have often reported low testosterone and SHBG to be associated with type 2 DM and the metabolic syndrome (MetS). Our objective was to determine the impact of metabolic syndrome and diabetic parameters on testosterone and SHBG in both MetS subjects and type 2 DM patients. Methods In this study, 120 Yemeni male aged 30–70 years old were enrolled, 30 of whom were healthy subjects with BMI < 25 kg/m2 that served as control, 30 MetS, 30 type 2 DM without MetS, and 30 type 2 DM with MetS according to IDF criteria. Results Testosterone (free and total) and SHBG were significantly lower in MetS subjects and modestly reduced in type 2 DM with and without MetS. Stepwise linear regression showed free and total testosterone to be negatively affected by waist circumference, and univariate analysis shows this significant difference to disappear when adjusted for waist circumference. On the other hand, stepwise linear regression showed SHBG to be positively affected by testosterone and age and negatively affected by FBG and TG. Univariate analysis shows this observed significant difference to disappear when adjusted for testosterone. Conclusion Abdominal obesity is a major determinant of low testosterone levels irrespective of diabetes status. Thus, supporting evidence suggesting that the causative relationship between the often low testosterone and type 2 DM might be bidirectional or even multidirectional and interrelated with obesity, MetS, and IR.

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.