Molecular characterization of glucose-6-phosphate dehydrogenase gene defect in the Kuwaiti population.

CONTEXT: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common human enzyme deficiencies. More than 130 different molecular abnormalities have been described worldwide, with considerable variation in the enzyme among various racial groups. Data from Kuwaiti populations are scarce, and the studies available are the result of screening male blood donors who may not be truly representative of the Kuwaiti population. OBJECTIVE: The objective of this study was to investigate the mutation spectrum of the G6PD gene among Kuwaiti Arabs. DESIGN: DNA was extracted from 82 G6PD-deficient Kuwaiti subjects (75 men and 7 women) and screened for gene mutations using polymerase chain reaction/restriction fragment length polymorphism and polymerase chain reaction/single-strand conformation polymorphism followed by direct sequencing. A total of 1209 randomly selected Kuwaiti adult subjects of both sexes were then screened for any characterized mutation. RESULTS: G6PD Mediterranean(563C-->T), and A-(202G-->A,376A-->G) genotypes were characterized as the most common variants among the G6PD-deficient population, representing 0.742 and 0.124 allele frequencies, respectively. The 2 previously described mutations, G6PD Chatham(1003G-->A) and Aures(143T-->C), were found at lower frequencies (0.101 and 0.034, respectively). The allele frequencies for these 4 G6PD variants among the randomly selected Kuwaitis were 0.035, 0.0074, 0.0046, and 0.0023 for Mediterranean, A-, Chatham, and Aures, respectively. CONCLUSION: This study has characterized the molecular heterogeneity of G6PD variants among ethnic Kuwaitis. The findings suggest that gene flow from the Indian subcontinent, sub-Saharan African, and other parts of the Mediterranean may have contributed to the observed G6PD mutations seen in the Kuwaiti population.

Lymphocyte subsets in healthy adult Kuwaiti Arabs with relative benign ethnic neutropenia.

Relative and absolute neutropenia is frequently seen in the healthy adult Kuwaiti Arab population. Fluorescent monoclonal antibody labelling followed by flow cytometry was used to determine the lymphocyte subsets in 48 normal healthy individuals in the Kuwaiti adult population (24 males and 24 females, age 17-59 years) with relative or absolute neutropenia, and this was compared to age-matched controls (64 males and 63 females). The mean haemoglobin levels were 13.6+/-1.5 and 13.7+/-1.5 g/dl in the neutropenic and control groups, respectively. White blood cell counts, absolute neutrophil and lymphocyte counts in neutropenic individuals with the corresponding reference range, taken from the control subjects (in parenthesis) were: WBC, 6.7+/-1.6 x 10(9)/l (4-10.4 x 10(9)/l), neutrophils, 2.7+/-0.8 x 10(9)/l (1.87-6.63 x 10(9)/l), lymphocytes, 3.3+/-0.9 x 10(9)/l (1.4-3.62 x 10(9)/l). Absolute values of lymphocytes, CD2+, CD3+, CD19+, CD4+, CD8+, HLADR+ and CD45RA+ cells were significantly higher in the neutropenic group. The range of values with the corresponding reference ranges, in parenthesis, were: CD2+, 1.61-4.30 x 10(9)/l (0.95-2.99 x 10(9)/l), CD3+, 1.37-4.16 x 10(9)/l (0.83-2.71 x 10(9)/l), CD19+, 0.16-1.09 x 10(9)/l (0.05-0.61 x 10(9)/l), CD4+, 0.70-2.89 x 10(9)/l (0.45-1.65 x 10(9)/l), CD8+, 0.57-1.80 x 10(9)/l (0.29-1.17 x 10(9)/l), HLADR+ 0.27-1.74 x 10(9)/l (0.02-0.62 x 10(9)/l), CD45RA, 0.90-4.63 x 10(9)/l (0.34-2.05 x 10(9)/l), respectively. The levels of natural killer cells, CD56+ cells were significantly lower compared to controls while the values of memory T lymphocytes, CD45RO+ were comparable to controls. These results indicate that difference in the leukocyte subpopulations may also be indicative of differences in the lymphocyte subpopulations and that reference ranges for these cell types in healthy neutropenic and non-neutropenic individuals should be established.

Reference values of lymphocyte subsets in the normal healthy adult Kuwaiti Arab population.

Fluorescent monoclonal antibody labelling followed by a lysed whole blood method and flow cytometry was used to determine the lymphocyte subpopulations in 127 (64 males and 63 females) normal healthy individuals in the adult (age 18-59 years) Kuwaiti population. Relative percentages and absolute values of CD2+, CD3+, CD19+, CD4+, CD8+, HLADR+, CD56+, CD45RO+, and CD45RA+ cells were determined. The reference ranges were CD2+, 73-92% (0.95-2.99 x 10(9) per l), CD3+, 64-85% (0.83-2.71 x 10(9) per l), CD19+, 6-22% (0.05-0.61 x 10(9) per l), CD4+, 34-54% (0.45-1.65 x 10(9) per l), CD8+, 20-42% (0.29-1.17 x 10(9) per l), HLADR+, 4-23% (0.02-0.62 x 10(9) per l), CD56+, 4-22% (0.06-0.58 x 10(9) per l), CD45RO+, 16-53% (0.26-1.42 x 10(9) per l) and CD45RA+, 35-72% (0.34-2.05 x 10(9) per l). The mean CD4/CD8 ratio was 1.50+/-0.35. CD3+ cells were positively correlated to both CD4+ and CD8+ cells (P<0.001), and CD4+ cells showed a significant positive correlation with CD8+ cells (P<0.001).