Polymorphisms within the angiotensinogen gene (GT-repeat) and the risk of stroke in pediatric patients with sickle

D C Tang1, R Prauner, W Liu

  • 1Molecular and Clinical Hematology Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.

Insights

Genetic markers for stroke risk in sickle cell disease (SCD) are needed. This study found specific GT-repeat alleles in the angiotensinogen (AGT) gene significantly increase stroke risk in pediatric SCD patients.

Area of Science:

  • Hematology
  • Genetics
  • Pediatrics

Background:

  • Stroke is a major complication in sickle cell disease (SCD).
  • Current methods lack reliable molecular or genetic markers for predicting stroke risk in SCD patients.
  • Previous research suggested relative hypertension as a potential risk factor.

Purpose of the Study:

  • To investigate the association between GT-repeat polymorphism in the angiotensinogen (AGT) gene and stroke risk.
  • To identify potential genetic markers for stroke risk assessment in pediatric SCD.
  • To evaluate the impact of specific AGT gene GT-repeat alleles on stroke occurrence.

Main Methods:

  • A case-control study involving 63 pediatric patients with SCD (21 stroke cases, 42 controls).
  • Genotyping of the GT-repeat polymorphism within the AGT gene.
  • Statistical analysis to compare genotype and allele distributions between stroke and non-stroke groups.

Main Results:

  • Significant differences in AGT gene GT-repeat genotype distribution were observed between stroke and non-stroke SCD patients (chi(2) = 10.82, P < 0.05).
  • Carriage of GT-repeat alleles A3 and/or A4 in the AGT gene was associated with a four-fold increased risk of stroke (OR = 4, P < 0.05).
  • Attributable odds ratios for alleles A3 and A4 were 2.24 and 4.33, respectively (P < 0.005).

Conclusions:

  • GT-repeat polymorphism within the AGT gene is associated with stroke risk in pediatric patients with SCD.
  • The presence of AGT gene alleles A3 and/or A4 significantly elevates the relative risk of stroke.
  • AGT gene GT-repeat genotyping may serve as a valuable genetic marker for assessing stroke risk in SCD patients, pending validation in larger cohorts.

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