BACKGROUND AND PURPOSE: To identify, using a genetic model, a key role for the renin-angiotensin system (RAS) in the development of dyscirculatory encephalopathy (DE) in Chernobyl cleanup workers (CCW). The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene denotes a substantial individual variation in RAS activity with the D-allele being associated with higher ACE activity. METHODS: Ninety-three male, Caucasian CCW were recruited from those under regular review at the All-Russia Centre of Emergency and Radiation Medicine, St. Petersburg. The presence or absence of DE was determined using existing institutional guidelines. ACE genotype was determined using internationally accepted methodologies. RESULTS: Angiotensin-converting enzyme genotype distribution in 59 subjects with DE was II: 10 (17%), ID: 31 (53%), DD: 18 (30%), D-allele frequency 56.8%. Whereas in those without the condition the distribution was II: 12 (35%), ID: 19 (56%), DD 3 (9%) and D-allele frequency 35.9% (P = 0.02). CONCLUSIONS: These data are the first to identify an association between the ACE D-allele and DE in CCW. They provide evidence of a significant role for the RAS in the development of DE and suggest that clinical trials of ACE inhibition would be profitable in this group.
BACKGROUND AND PURPOSE: To identify, using a genetic model, a key role for the renin-angiotensin system (RAS) in the development of dyscirculatory encephalopathy (DE) in Chernobyl cleanup workers (CCW). The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene denotes a substantial individual variation in RAS activity with the D-allele being associated with higher ACE activity. METHODS: Ninety-three male, Caucasian CCW were recruited from those under regular review at the All-Russia Centre of Emergency and Radiation Medicine, St. Petersburg. The presence or absence of DE was determined using existing institutional guidelines. ACE genotype was determined using internationally accepted methodologies. RESULTS:Angiotensin-converting enzyme genotype distribution in 59 subjects with DE was II: 10 (17%), ID: 31 (53%), DD: 18 (30%), D-allele frequency 56.8%. Whereas in those without the condition the distribution was II: 12 (35%), ID: 19 (56%), DD 3 (9%) and D-allele frequency 35.9% (P = 0.02). CONCLUSIONS: These data are the first to identify an association between the ACE D-allele and DE in CCW. They provide evidence of a significant role for the RAS in the development of DE and suggest that clinical trials of ACE inhibition would be profitable in this group.
Authors: Tammy C Lee; Dana Greene-Schloesser; Valerie Payne; Debra I Diz; Fang-Chi Hsu; Mitra Kooshki; Rashida Mustafa; David R Riddle; Weiling Zhao; Michael D Chan; Mike E Robbins Journal: Radiat Res Date: 2012-06-12 Impact factor: 2.841