Association of cytochrome P450, glutathione S-transferase and N-acetyl transferase 2 gene polymorphisms with incidence of acute myeloid leukemia.

The objective of the paper was to study the association of polymorphisms of phases I and II xenobiotic metabolizing enzyme genes cytochrome P450 (CYP-4501A1*2A, *2B, *2C and *4 alleles, CYP-4502D6*4 allele), glutathione-S-transferase (GSTM1 and GSTT1 null genotypes) and N-acetyl transferase 2 (NAT2*6B and *7A alleles) with the incidence of acute myeloid leukemia (AML) in an eastern Indian population. Polymerase chain reaction and restriction fragment length polymorphism of genomic DNA from peripheral blood cells were used to detect CYP-450 and NAT2 gene polymorphisms in 110 AML patients and 144 racially and geographically matched normal controls. Polymerase chain reaction was also applied to detect GST gene polymorphisms in both groups. A statistically significant difference between the AML group and the normal group was observed in the case of glutathione-S-transferase M1 null (odds ratio 3.25, 95% confidence interval 1.9-5.58, P<0.001) and N-acetyl transferase 2*6B (odds ratio 3.04, 95% confidence interval 1.79-5.16, P<0.001) genotypes. Combined deficiency of N-acetyl transferase 2 and glutathione-S-transferase M1 genes produced an odds ratio of 11.91 (95% confidence interval 4.06-34.96, P<0.001). The effect of N-acetyl transferase 2*6B (P<0.001) is significant only at ages

A study on endocrine dysfunction in thalassaemia.

The aim was to study the prevalence and severity of hormonal imbalance affecting growth, gonadal and thyroid function in thalassaemic patients and to find out whether any correlation exists between the degree of tissue iron-overload and several patients characteristics like age, gender, foetal haemoglobin (HbF) level, type of thalassaemia (beta or E-beta), and the presence of specific endocrine abnormality. Sixty-eight consecutive non-chelated, transfusion-dependent patients of beta and E-beta-thalassaemia with significant tissue iron overload (serum ferritin more than 2000 microg/l) were included. Standing height was noted and clinical features of hypogonadism were recorded. Insulin tolerance test was done to assess growth hormone reserve. Serum oestradiol, T3,T4,TSH were measured in fasting clotted sample, while pooled sera (from 3 consevutive morning samples) was used for testosterone, FSH and LH. Hypogonadism was the commonest abnormality, both in males (52.28%) and females (35.89%) followed by growth retardation (20.58%) and reduced growth hormone reserve (7.35%). There was no significant difference in the prevalence of endocrine dysfunction with regard to patient's age, gender, type of thalassaemia (beta or E-beta) amd HbF level. Hypogonadic females had a significantly elevated mean serum ferritin level. Subclinical hypothyroidism was present in 23.52% of patients, related to the duration of disease. No association was found between pituitarty and thyroid dysfunction.

A novel 33.3 kb deletion (- -KOL) in the alpha-globin gene cluster: a brief report on deletional alpha-thalassaemia in the heterogeneous eastern Indian population.

We have detected, in three unrelated eastern Indian individuals, a hitherto unreported alpha zero deletion, - -KOL, in the heterozygous state, encompassing the embryonic zeta2-globin and the duplicated alpha-globin genes extending from c. 1150 bp upstream of the zeta2 globin gene to c. 960 bp downstream of the theta1 gene. Other deletions present in 120 unrelated, eastern Indian, putative alpha-thalassaemia patients are -3.7 kb (16.25%), -4.2 kb (5%) and - -SEA (3.33%).