Frequency of the 677 C→T mutation of the methylenetetrahydrofolate reductase gene among Kuwaiti sickle cell disease patients

Abstract

Sickle cell disease (SCD) is relatively mild among Kuwaiti Arabs. However, an atypical subset of patients exists with frequent, severe vaso-occlusive crisis and osteonecrosis. The thermolabile variant of MTHFR, resulting from a C→T mutation at nucleotide 677, has been shown to be associated with hyperhomocysteinemia, which is an important risk factor for premature vascular disease. We have screened an unselected group of 41 Kuwaiti SCD patients (33 SS and 8 S␤ 0 -thal) attending the Hematology Clinic of Kuwait University Teaching Hospital for the MTHFR mutation, using a PCR-RFLP method. The patients were aged 2-41 years (mean of 12.8 ± 8.6). One (2.4%) individual was homozygous for the mutation while 15 (36.6%) were heterozygous, giving an allele frequency of 20.7%. Twenty-one patients (14 SS and 7 S␤ 0 -thal) were screened for osteonecrosis using MRI of the hip (spin-echo T1-and T2-weighted images). Seven (33.3%) had varying degrees of osteonecrosis, among whom the frequency of the 677 C→T allele was 21.4%. The frequency was identical among those without osteonecrosis. Although the allele frequency is higher among our patients compared to American SS patients, our results do not suggest an association with osteonecrosis. Am.

Sickle Cell Disease in the Post Genomic Era: A Monogenic Disease with a Polygenic Phenotype

“…This gene has been found associated with this phenotype in a large number of patients of the CSSCD population but could not be confirmed in the Kuwaiti population 78. This suggests that different genetic factors may be operative in different populations.…”

Association of sickle avascular necrosis with bone morphogenic protein 6

“…In AVN, the progressive degeneration of bone eventually leads to its collapse and destruction of the articular Allele frequencies between the AVN group and the non-AVN group were compared using Pearson's chi-square statistical analysis with one degree of freedom; '-' denotes that the SNP assay did not work a The SNP was also genotyped by Baldwin et al [1] cartilage, supporting a role for BMP6 in the pathogenesis of this complication. Association studies which examined polymorphisms in MTHFR [5], platelet glycoprotein IIIa (ITGB3) [6], and plasminogen activator inhibitor-1 (PAI-1) [7] with AVN in SCD in small numbers were non-conclusive. Another study sought association of combined vaso-occlusive complications including stroke, acute chest syndrome, AVN, and priapism with polymorphisms in candidate genes [8].…”

β-Globin Gene Cluster Haplotype Analysis as a Predictor of Sickle Cell Disease Severity

“…Many factors are known to contribute to this variance in disease severity, including the level of fetal hemoglobin (HbF), presence of α-thalassemia, and the type of haplotype linked to the β-globin gene cluster. [2][3][4][5] Symptoms associated with the disease include severe anemia (hemolytic and aplastic), susceptibility to infections, organ injury, sequestration, and episodic vaso-occlusions. 4 Death in most patients has been attributed to acute chest syndrome, chronic organ damage (such as renal and cardiac failure), cerebrovascular accident, and complications of pregnancy.…”