rs2229169

This is a good proxy for alpha-2B-adrenergic receptor gene (ADRA2B) deletion polymorphism (del301–303; rs4066772). The minor rs2229169 allele was in a strict linkage disequilibrium with the deletion of three amino acids in ADRA2B (Ins/Del301-303) in a mixed African–American/white group and in a large Chinese study . Alpha-2B adrenergic receptors contribute to norepinephrine stimulation in the brain and to peripheral vasoconstriction. The deletion polymorphism del301–303 encodes a version of the receptor that, unlike normal alpha-2B receptors, fails to decrease its activity (desensitize) in response to prolonged stimulation . This may result in both negative cardiovascular consequences and positive cognitive effects. A large population cohort of Finnish middle-aged men (1606 men, mean age at the start 53 years) was followed for the average time of 18 years. Acute coronary events defined as hospitalizations for myocardial infarction or prolonged acute chest pain were more frequent in the men with del301–303 polymorphism: Del/Del OR=1.57 (P=0.002), Del/Ins OR=1.25 (P=0.077), Ins/Ins OR=1. Associations with the number of sudden cardiac deaths and overall cardiac heart disease mortality were also observed, but they would not be significant after correcting for multiple comparisons. A study of Koreans compared more than 600 patients hospitalized for an ischemic stroke with control subjects. The deletion polymorphism conferred higher risk of ischemic stroke: Del/Del OR=1.78 (P=0.007), Del/Ins OR=1.25 (P=0.107), Ins/Ins OR=1. Association of the deletion genotype with small-vessel disease was the main contributor to the risk. In a study of more than 400 young Swiss adults, the carriers of del301–303 polymorphism had about 20% better memory for emotional photographs, both positive and negative. This enhancement of emotional memory was selective: the level of emotions caused by the photographs, the memory for neutral photographs, working memory, and attention were not dependent on genotype. Among the Rwandan genocide refugees, the same authors found the deletion to be associated with increased re-experiencing of traumatic events but independently from PTSD, which was distributed equally among the genotypes. Homozygous rs2229169 Chinese subjects, being by extension del301–303 homozygotes, also had about 20% better (shorter) reaction time in a stop-go cognitive test as compared to wild-type homozygotes.