[Show abstract][Hide abstract] ABSTRACT: Thyroid gland dysfunction and echocardiographic cardiac abnormalities are well-documented in patients with transfusion dependent beta-thalassemia major (β-TM).
This cross-sectional analytic study was conducted to investigate left ventricle (LV) diastolic and systolic function using pulsed Doppler (PD) and tissue Doppler (TD) echocardiography and correlate that with serum level thyroid stimulating hormone in patients with β-TM.
The study was conducted on patients with β-TM (n = 110, age 15.9 ± 8.9 years) and compared with a control group (n = 109, age 15.8 ± 8.9 years). In all participants, echocardiographic indices of PD and TD were performed and blood samples were withdrawn for measuring the serum level of TSH, free T4, and ferritin. A linear regression analysis was performed on TSH level as the dependent variable and serum ferritin as independent. Stepwise multiple regression analysis was used to determine the odds ratio of different biochemical and echo variables on the risk of developing hypothyroidism.
Patients with β-TM compared with controls had thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm/M(2), P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm/m(2), P < 0.01) and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm/m(2), P < 0.001). In addition, β-TM patients had higher transmitral E wave velocity (E) (70.81 ± 10.13 vs. 57.53 ± 10.13 cm/s, P = 0.02) and E/A ratio (1.54 ± 0.18 vs. 1.23 ± 0.17, P < 0.01) and shorter deceleration time (DT) (170.53 ± 13.3 vs. 210.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em) was significantly higher in the β-TM group (19.68 ± 2.81 vs. 13.86 ± 1.41, P < 0.05). The tissue Doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in the β-TM group compared with controls with Sm, 4.82 ± 1.2 vs. 6.22 ± 2.1 mm/sec, P < 0.05 and (Em), 3.51 ± 2.7 vs. 4.12 ± 2.5 mm/sec. P < 0.05, respectively). The tricuspid valve velocity was significantly higher in β-TM patients compared with controls 2.85 ± 0.56 vs. 1.743 ± 0.47 m sec, respectively, P < 0.01). The prevalence of subclinical hypothyroidism in patients with β-TM was 15.4%, with significantly higher mean serum TSH compared with controls (6.78 ± 1.5 vs. 3.10 ± 1.02 μIU/mL, P < 0.01) and positively correlated with the serum ferritin level (r = 0.34, P = 0.014). On multiple regression analysis, the LV mass, LVEF%, and E/A ratio were not positive predictors of hypothyroidism in patients with β-TM.
We conclude that patients with β-TM had a high prevalence of subclinical hypothyroidism of 15.4%. Thyroid stimulating hormone was significantly high and positively correlated with the serum ferritin level. Echo cardiographic pulsed Doppler showed a restrictive LV diastolic pattern suggestive of severe diastolic dysfunction with preserved left ventricle systolic function.
Clinical Medicine Insights: Cardiology 01/2013; 7:21-7. DOI:10.4137/CMC.S10702
[Show abstract][Hide abstract] ABSTRACT: The association of vascular endothelial growth factor (VEGFA) variants and VEGF secretion with sickle cell disease (SCD) vasoocclusive crisis (VOC) was investigated in 210 VOC patients and 114 pain-free control patients.
VEGFA -2578C/A (rs699947), -460T/C (rs833061), -1154G/A (rs15703060), -634G/C (rs2010963), 398G/A (rs833068), 497G/A (rs833070), -583T/C (rs3025020), and 936C/T (rs3025039) were carried out by real-time PCR.
Higher frequency of rs2010963 C-allele, rs833068 A-allele, and rs3025020 C-allele and significant differences in rs2010963, rs833068, and rs3025020 genotype distribution were seen in VOC than steady-state patients. Increased VOC risk was seen with rs2010963 as heterozygous and more as homozygous, and in rs833068 and rs3025020 homozygous carriers. While there were no differences in VEGF levels between VOC and steady-state controls, there was a progressive decline in serum VEGF in rs2010963 and rs833068 heterozygous and homozygous genotypes, but an opposite trend was seen in VOC patients. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs833068, and rs833070, but weak or no LD between rs3025020 and rs3025039 and other SNPs. Six-locus (rs699947/rs833061/rs1570360/rs2010963/rs833068/rs833070) VEGFA haplotype analysis identified haplotype 111111 to be negatively (OR = 0.68) and haplotype 111222 to be positively (OR = 1.89) associated with VOC. rs2010963, rs833068, and rs3025020 were correlated with VOC type, while rs3025020 was correlated with hospitalization, VOC treatment, and duration.
Specific VEGFA variants contribute to the pathogenesis of SCD VOC.
European Journal Of Haematology 08/2012; 89(5):403-9. DOI:10.1111/ejh.12003 · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) vaso-occlusive crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P=0.03), rs3024719 (P=0.02), rs3024731 (P<0.001), and rs3024735 (P<0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P=0.028) and rs3024735 (P=0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P=0.024), AGAA (P=0.011), and GGTG (P=0.002), and reduced frequency of AGTG haplotype (P=0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (P(c)=0.001) and GGTG (P(c)=0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.
Annals of Hematology 05/2012; 91(8):1215-20. DOI:10.1007/s00277-012-1474-6 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chelating therapy in transfusion-dependent patients with β-thalassemia major (β-TM) is mandatory to reduce the toxic effect of iron on the myocardium.
To evaluate the impact of low and high dose of oral chelating therapy (deferasirox) on pulsed and tissue echocardiographic indices in patients with β-TM.
This interventional study conducted on patients with transfusion-dependent β-TM (n=38) on deferasirox 20 mg/kg/d medication, group (DFX-20) for at least 6 months, followed by administration of a higher dose of deferasirox, 40 mg/kg/d, group (DFX-40) for another 6 months. Pulsed and tissue Doppler echocardiography carried out at the beginning and at the end of treatment interval (6 months) for both groups, with monthly blood analysis of serum ferritin, alanine transaminase, hemoglobin, and creatinine. An age-matched control group of 38 patients was evaluated for echo Doppler blood analysis.
Patients of group DXF-40 compared with group DFX-20, the tissue Doppler echocardiogram showed lower E/Em ratio (16.01 ± 2.85 vs. 19.68 ± 2.81, P<0.05), higher systolic wave velocity (Sm) (5.87 ± 1.40 vs. 4.80 ± 1.20, P<0.05), and higher early diastolic wave (Em) velocity (4.25 ± 1.70 vs. 3.50 ± 1.80, P<0.05), respectively. Patients in group DFX-20, compared with control group, had M-Mode echo with thicker left ventricle (LV) septal wall (P<0.001) and posterior wall (P<0.01), higher left ventricle end diastolic diameter index (P<0.05). The pulsed Doppler echocardiogram showed a higher LV transmitral E wave velocity (P<0.05), higher E/A ratio (P<0.01), and the duration of deceleration time was significantly shorter (P<0.01). There were no significant changes observed in the left ventricle ejection fraction percentage (LVEF%) or fractional shortening between both treatment groups. Serum ferritin was significantly lower in DFX-40 group compared with DFX-20 β-TM group (338). There was a significant positive correlation between the serum ferritin and the E/Em ratio (r=0.31, P<0.001). The tricuspid valve velocity was significantly higher in β-TM patients compared with the control group (P<0.05).
The increment of oral deferasirox as chelating therapy in β-TM patients to 40 mg/kg/d over 6 months duration showed a significant increments of systolic and diastolic tissue Doppler velocities with a significant reduction of E/Em ratio in comparison with 20 mg/kg/d. There were no changes of LVEF. A longer duration of follow-up may be justified in such group of patients.
European Journal Of Haematology 05/2011; 87(3):267-73. DOI:10.1111/j.1600-0609.2011.01641.x · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients; however, its mechanisms are poorly understood. In view of their prothrombotic nature, we hypothesized that SCA-associated VOC may be due to the presence of anti-annexin V antibodies. Anti-annexin V antibodies were measured with ELISA in 177 VOC and 81 steady-state SCA patients. Anti-annexin V IgM and IgG concentrations were significantly higher in VOC patients than in steady-state patients and were associated with elevated VOC risk. After categorizing anti-annexin V antibodies, the adjusted odds ratio increased as the percentile value increased. Monovariate logistic regression analysis demonstrated a positive dose-effect relationship for anti-annexin V IgM with VOC, with increased VOC risk seen with increased antibody titers. Multivariate logistic regression analyses confirmed the association of anti-annexin V IgM, more so than IgG, as an independent VOC risk factor. Anti-annexin V IgG antibodies correlated positively with VOC type and negatively with HbF and age of VOC onset, while anti-annexin V IgM correlated positively with VOC type, duration, frequency, site, pain severity, hospitalization, and medication, and negatively with age of VOC onset and HbS levels. High levels of anti-annexin V IgM antibodies constitute a risk factor for VOC in SCA patients.
Annals of Hematology 02/2011; 90(9):1031-6. DOI:10.1007/s00277-011-1184-5 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Doppler echocardiographic studies of the left ventricle (LV) function in patients with β-Thalassemia Major (β-TM) had shown different patterns of systolic and diastolic dysfunctions associated with abnormal serum brain natriuretic peptide (BNP).
This cross-sectional study was designed to study the LV systolic and diastolic functions and correlate that with serum level of N-terminal pro brain natriuretic hormone (NT- pro BNP) in patients with β-TM using Pulsed Doppler (PD) and Tissue Doppler (TD) echocardiography.
The study was conducted on patients with β-TM (n = 38, age 15.7 ± 8.9 years) and compared with an age-matched controls (n = 38, age 15.9 ± 8.9 years). In all participants, PD and TD echocardiography were performed and blood samples were withdrawn for measuring the serum level of NT-pro BNP, ferritin, and alanine transaminase.
Patients with β-TM compared with controls, have thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm, P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm, P < 0.01), and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm, P < 0.001). In addition, β-TM patients have higher transmitral E wave velocity (E) (70.818 ± 10.139 vs. 57.532 ± 10.139, p = 0.027) and E/A ratio (1.54 ± 0.17 vs. 1.23 ± 0.19, P < 0.01) and shorter deceleration time (DT) (160.13 ± 13.3 vs. 170.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em(-)) was significantly higher in β-TM group (19.6 ± 2.81 vs. 13.868 ± 1.41, P < 0.05). The tissue doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in β-TM group compared to controls (Sm: 4.82 ± 1.2 vs. 6.22 ± 2.1 mm/sec, P < 0.05; Em: 3.51 ± 2.7 vs. 4.12 ± 2.5 mm/sec P < 0.05, respectively). The tricuspid valve velocity was significantly higher in β-TM patients compared with controls (2.993 ± 0.569 vs. 1.93 ± 0.471 m/sec, respectively, P < 0.01). The mean serum NT pro-BNP in β-TM was significantly higher compared with controls (37.6 ± 14.73 vs. 5.5 ± 5.4pg/ml, P < 0.05). The left ventricle ejection fraction (EF%) and fractional shortening (FS%) were not significantly different between both groups.
We conclude that patients with β-TM had a significantly higher serum level of NT-pro BNP that is positively correlated with the E/Em ratio on tissue Doppler. Furthermore, we confirm our previous findings that patients with β-TM exhibit LV diastolic pattern on echocardiogram suggestive of restrictive type with well preserved left ventricle systolic function.
Clinical Medicine Insights: Cardiology 12/2010; 4:135-41. DOI:10.4137/CMC.S6452
[Show abstract][Hide abstract] ABSTRACT: In view of evidence linking sickle cell anemia (SCA) with chronic inflammation, and given the role of high sensitivity C-reactive protein (hs-CRP) as inflammatory mediator, we hypothesized that SCA vasoocclusive crisis (VOC) is associated with heightened hs-CRP levels. Study subjects comprised 104 SCA patients who experienced VOC event during the study period (VOC group), and 40 SCA patients who did not develop VOC for at least 9 months prior to blood collection (Steady-state group). hs-CRP determination was done by latex-enhanced nephelometry. Higher hs-CRP levels were seen in VOC [median(range)=31.3(1.14-363.0)] than steady-state [median(range)=5(0.16-185.0)] groups (P<0.001), with enrichment in high hs-CRP percentiles in VOC cases, which translated into step-wise increased VOC risk. Receiver-operating characteristic (ROC) analysis was employed in assessing the usefulness of hs-CRP as predictor of the frequency and severity of VOC. Spearman's correlation coefficient between hs-CRP and VOC was 0.65 (P<0.001) among unselected patients (0.71 in males and 0.59 in females). hs-CRP area under ROC curves was 0.90 (95% CI=0.85-0.94) among unselected patients, 0.94 (95% CI=0.89-0.98) for males, and 0.85 (95% CI=0.77-0.93) for females. Logistic regression analysis confirmed the positive association of increased hs-CRP levels with VOC, which correlated positively with VOC frequency (P<0.001), type (P<0.001), pain (P<0.001), and need for hospitalization (P=0.024). These data support strong association of increased hs-CRP levels with VOC, which impacts VOC-related parameters, and support a role for hs-CRP in VOC follow-up.
[Show abstract][Hide abstract] ABSTRACT: We investigated the association of sickle cell anemia (SCA) vaso-occlusive crisis (VOC) with depression, anxiety, and stress disorders among Bahraini patients and controls. This was a cross-sectional study that involved administering Depression Anxiety Stress Scales (DASS-21) consisting of structured depression, anxiety, and stress scales to SCA patients with (n=138) and without (n=105) VOC. Multinomial regression and correlation analysis were used in assessing the association of VOC with depression and/or anxiety and/or stress, after adjusting for other covariates. Significantly higher proportion of VOC patients was found among the severe-extremely severe anxiety (P<0.002) and stress (P=0.001) groups; the frequency of depressed patients was comparable between the 2 groups. Adjusting for age, sex, income, number of affected individuals per family, and HbS levels, mild-moderate (P=0.042; odds ratio=2.00; 95% confidence interval=1.03-3.91) and severe-extremely severe (P=0.004; odds ratio=4.43; 95% confidence interval=1.59-12.34) anxiety were independently associated with VOC. Both depression and stress were not associated with VOC after adjusting for these covariates. These results suggest a positive contribution of VOC to the increased rates of anxiety disorders among SCA patients, thereby recommending counseling SCA patients with repeated VOC for these psychologic comorbidities, in particular anxiety.
[Show abstract][Hide abstract] ABSTRACT: Doppler echocardiographic studies in patients with beta-Thalassemia Major (beta-TM) had shown different patterns of left ventricle (LV) systolic and diastolic dysfunctions.
This cross-sectional study was designed to study the LV systolic and diastolic function in patients with beta-TM using Pulsed Doppler (PD) Echocardiogram and assess the QTc interval and QT dispersion (QTd) on 12 leads ECG.
All patients were evaluated clinically as well as by echocardiography and 12 leads ECG. The study included patients with beta-TM (n = 38, age 15.7 +/- 8.9 years), compared with an age-matched healthy control group (n = 38, age 15.9 +/- 8.9 years).
In 38 patients with beta-TM Compared with healthy control group, The QTc interval and the QTd dispersion on ECG were increased with no significant difference mode echo showed that beta-TM patients have thicker LV septal wall index (0.659 +/- 0.23 vs. 0.446 +/- 0.219 cm/M(2), P < 0.001), posterior wall index (0.659 +/- 0.235 vs. 0.437 +/- 0.214 cm/M(2), P < 0.01), and larger LVEDD index is (3.99 +/- 0.48 vs. 2.170 +/- 0.57 cm/M(2). P < 0.05). Pulsed Doppler showed high LV trans-mitral E wave velocity index (70.818 +/- 10.139 vs. 57.532 +/- 10.139, P < 0.05) and E/A ratio (1.54 vs.1.23, P < 0.01). The duration of deceleration time index (DT) and isovolumic relaxation time index (IVRT) were significantly shorter in patients with beta-TM (150.234 +/- 20.0.23 vs. 167.123 +/- 167.123 +/- 19.143 msec/M(2), P < 0.01) and (60.647 +/- 6.77 vs. 75.474 +/- 5.83 msec/M(2), P < 0.001), respectively. The tricuspid valve velocity in patients with beta-TM was significantly higher than controls (2.993 +/- 0.569 vs. 1.93 +/- 0.471 m/sec, respectively, P < 0.01), with calculated pulmonary artery pressure of 2.4 times the control (36.0 vs. 14.8 mmHg). However, the LVEF% or fractional shortening were not significantly different.
In this study, beta-thalassemia major patients compared with controls have differences of QT dispersion and corrected QT interval that is of no statistical significance. A significantly thicker LV wall and LV diastolic filling indices are suggestive of restrictive diastolic pattern. These data indicate that LV diastolic abnormalities compromised initially in patients with beta-thalassemia major.
Clinical Medicine Insights: Cardiology 03/2010; 4:31-7.
[Show abstract][Hide abstract] ABSTRACT: Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients. Insofar as polymorphism in human platelet alloantigen (HPA) exhibit a prothrombotic nature, we hypothesized that specific HPA polymorphic variants are associated with VOC. We investigated the distribution of HPA1, HPA2, HPA3, HPA4, and HPA5 alleles genotypes among VOC and non-VOC control SCA patients.
This was a case-control study. Study subjects comprised SCA patients with (VOC group; n = 127) or without (Steady-state group; n = 130) VOC events. HPA genotyping was done by PCR-SSP.
Significantly higher frequencies of HPA-2b, HPA-3b, and HPA-5b alleles, and marked enrichment of HPA-3b/3b, HPA-5a/5b, and HPA-5b/5b genotypes, were seen in VOC than in control SCA patients. Taking homozygous wild-type genotypes as reference, univariate analysis identified HPA-3a/3b, HPA-3b/3b, and HPA-5b/5b to be associated with VOC. Multivariate analysis confirmed the independent association of only HPA-3a/3b and HPA-3b/3b genotypes with VOC. HPA-3 genotypes were significantly correlated with VOC frequency, type, and medication, and requirement for hospitalization. While both HPA 3a/3b (P = 0.002; OR = 2.94; 95% CI = 1.49-5.77) and 3b/3b (P = 0.006; OR = 3.16; 95% CI = 1.40-7.17) genotypes were associated with need for hospitalization, only HPA-3b/3b was associated with VOC frequency, type (localized vs. generalized), and medication (narcotics vs. NSAIDs).
This confirms the association of HPA polymorphisms with SCA VOC, of which HPA-3 appears to be independent genetic risk factors for SCA VOC.
European Journal Of Haematology 09/2009; 83(6):579-85. DOI:10.1111/j.1600-0609.2009.01339.x · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the association of human leukocyte antigens (HLA) class II alleles and haplotypes with the pathogenesis of acute chest syndrome (ACS) in 186 sickle cell anemia (SCA) patients, of whom 58 had documented ACS (new pulmonary infiltrate, fever, and other associated clinical events) and 128 with a negative history of ACS, serving as controls. HLA DRB1* and -DQB1* genotyping was performed by polymerase chain reaction-sequence-specific priming. Of the DRB1* and DQB1* alleles analyzed, only DRB1*130101 (Pc < 0.001) was positively associated with ACS. DRB1*130101-DQB1*060101 haplotype was more prevalent among ACS patients (P = 0.018), thus conferring disease susceptibility. Specific HLA alleles and haplotypes may influence ACS risk in SCA patients, and specific HLA genotypes may be useful markers for identifying high-risk SCA ACS patients.
[Show abstract][Hide abstract] ABSTRACT: We investigated the association of human leukocyte antigens (HLA) class II alleles and haplotypes with the pathogenesis of acute chest syndrome (ACS) in 186 sickle cell anemia (SCA) patients, of whom 58 had documented ACS (new pulmonary infiltrate, fever, and other associated clinical events) and 128 with a negative history of ACS, serving as controls. HLA DRB1* and -DQB1* genotyping was performed by polymerase chain reaction–sequence-specific priming. Of the DRB1* and DQB1* alleles analyzed, only DRB1*130101 (Pc < 0.001) was positively associated with ACS. DRB1*130101-DQB1*060101 haplotype was more prevalent among ACS patients (P ¼ 0.018), thus conferring disease susceptibility. Specific HLA alleles and haplotypes may influence ACS risk in SCA patients, and specific HLA genotypes may be useful markers for identifying high-risk SCA ACS patients. Acute chest syndrome (ACS) is a major complication of sickle cell anemia (SCA); and a significant cause of morbidity and mortality (1, 2) and a leading cause of hospitalization among SCA patients (3, 4). While several etiologies have been proposed for the pathogenesis of ACS, the underlying cause remains unknown in most (50%) cases (1, 3). It has been suggested that infectious (Chlamydia pneumoniae and Myco-plasma pneumoniae) (4–6) and noninfectious (pulmonary infarction and fat embolism) (4, 6, 7) causes contribute to ACS development. ACS is a combination of respiratory symptoms and new pulmonary infiltrates (2, 4) and is accompanied by fever, cough, sputum production, or new-onset hypoxia, with repeated ACS episodes progressing to chronic lung disease and even death (2, 8). A number of risk factors have been documented in association with ACS, including younger age, low hemoglobin (Hb) levels, vaso-occlusive crisis (VOC; 3, 9), and high steady-state Hb levels, and leukocyte count (4, 7, 10).
[Show abstract][Hide abstract] ABSTRACT: We investigated the association of human leukocyte antigen (HLA) class II alleles and haplotypes with the pathogenesis of sickle cell anemia (SCA) osteomyelitis. SCA patients comprised 42 patients with osteomyelitis and 150 patients without osteomyelitis; HLA-DRB1* and HLA-DQB1* genotyping was performed by polymerase chain reaction-sequence-specific priming (SSP). DRB1*100101 (P value corrected for the number of different alleles tested, Pc=0.003) was positively associated with osteomyelitis. At the haplotype level, DRB1*100101-DQB1*050101 (Pc=0.001) was more prevalent among patients, while DRB1*030101-DQB1*0201 (Pc=0.020) and DRB1*040101-DQB1*0302 (Pc=0.039) were more prevalent among SCA controls, thereby conferring disease susceptibility or protection to these haplotypes, respectively. These results show that specific HLA haplotypes influence SCA osteomyelitis risk and that specific HLA types may serve as markers for identifying SCA patients at high risk for osteomyelitis.
[Show abstract][Hide abstract] ABSTRACT: The association of methylenetetrahydrofolate reductase (MTHFR) gene mutations, C677T and A1298C, together with changes in homocysteine (Hcy) levels was investigated in 106 sickle cell disease patients and 156 healthy controls from Bahrain. The mutation analysis was done by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). While the frequencies of the mutant alleles C677T and A1298C were comparable between patients and controls, the frequency of the A1298C (C/C) (p = 0.03) but not C677T (T/T) (p = 0.67) genotype, and of the 677T/1298C haplotype were significantly higher in the patients (p = 0.05). Homocysteine levels were normal in all subjects. This suggests that the A1298C, but not C677T, mutation is associated with the genotype of sickle cell disease.
[Show abstract][Hide abstract] ABSTRACT: This report describes clinical and laboratory features of a case of Chediak-Higashi syndrome that presented in the accelerated phase of the disorder. This female infant presented with a fever, marked neutropenia, large cytoplasmic granules in leukocytes and a constellation of features that suggested a virus-associated hemophagocytic syndrome. The clinical course was marked by limited response to the therapeutic agents that included ascorbate, cytotoxic agents and granulocyte colony-stimulating factor.
Saudi medical journal 05/2002; 23(4):464-6. · 0.59 Impact Factor