Association of BCL11A genetic variant (rs11886868) with severity in β-thalassaemia major & sickle cell anaemia.

Background & objectives: The amount of foetal haemoglobin that persists in adulthood affects the clinical severity of haemoglobinopathies including β-thalassaemia major and sickle cell anaemia (SCA). The present study was undertaken to analyse β-thalassaemia as well as SCA patients for the single nucleotide polymorphism (SNP), rs11886868 (T/C) in BCL11A gene and to evaluate the association between this polymorphism and severity of β-thalassaemia major and SCA. Methods: A total of 620 samples (420 β-thalassaemia major and 200 SCA cases) were analysed before blood transfusion using basic screening tests like complete blood analysis and osmotic fragility and further confirmed by high performance liquid chromatography (HPLC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot blot techniques. All patients were transfusion dependent. Patients with β-thalassaemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. β-thalassaemia as well as SCA patients were analysed for the SNP, rs11886868 (T/C) in BCL11A gene and association between this polymorphism and severity of β-thalassaemia major as well as SCA was evaluated. Results: There was a significant difference in genotypic and allelic frequencies of BCL11A gene polymorphism between mild and moderate and mild and severe cases in both the groups. A significant (P<0.001) difference was observed in the mean HbF levels between the three genotypes in different severity groups. HbF levels were found to be high in CC genotype bearing individuals followed by TC and TT in β-thalassaemia major as well as SCA. Interpretation & conclusions: This study confirms that the T/C variant (rs11886868) of the BCL11A gene causing downregulation of BCL11A gene expression in adult erythroid precursors results in the induction of HbF and ameliorates the severity of β-thalassaemia as well as SCA.

MTHFR Gene (C677t) Polymorphism in Ischemic Stroke, its Subtypes and Hemorrhagic Stroke in a South Indian Population.

Objective: We investigated the association of MTHFR C677T polymorphism with ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian Population from Andhra Pradesh. Methods: Six hundred and twenty ischemic stroke patients, 220 hemorrhagic stroke patients and 620 age and sex matched healthy controls, were included in the present study. The polymorphism was determined using PCR-RFLP technique. Results: The strength of association between genotypes and stroke types was measured by the odds ratio with 95% confidence interval and chi-squared analysis. We found significant association of the CT genotype with ischemic stroke as well as haemorrhagic stroke (p<0.05). Further, evaluating the association of this polymorphism with stroke subtypes, we found significant association with intracranial large artery (p<0.05), lacunar stroke (p<0.05) and undetermined etiology (p<0.05). However, there was no significant difference in genotypic or allelic frequencies between ischemic and hemorrhagic strokes. Conclusion: Our study suggests that MTHFR (C677T) is an important risk factor for ischemic stroke, its subtypes and hemorrhagic stroke in the South Indians from Andhra Pradesh but it cannot help in distinguishing between the two types of stroke.

ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population.

Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions between environmental factors and certain genetic factors. Genetic variants in the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been associated with abnormalities of serum lipid levels of high-density lipoprotein (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases, and this condition has been considered to be involved in the mechanism of insulin resistance (IR). Therefore, we investigated possible association between ABCA1 C69T gene polymorphism and T2DMin a Saudi population. This study was carried out with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. We observed that the frequency of the T allele of the ABCA1 C69T gene was significantly higher in healthy subjects compared to T2DMpatients (0.28 vs 0.45; p<0.0001; OR (95% CI) = 0.4624 (0.3732–0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.