Genetic Variation in Platelet Aggregation

Completed

Brief Summary: The aim of the study is to test whether genetic variation in the alpha 2A adrenergic receptor affects diurnal variation in platelet aggregation.

Detailed Description: There is a marked diurnal fluctuation in the occurrence of acute myocardial infarction and sudden death, with peak incidences occurring in the early morning. Platelet aggregation has also been shown to increase in the early morning. The investigators will test the hypothesis that alpha 2a-adrenergic receptor (ADRA2A) genetic variation, specifically haplotype 4, affects platelet aggregation. The investigators will compare diurnal platelet aggregation in haplotype 4 subjects with subjects in the other haplotype families. In addition, the investigators will compare platelet aggregation after the cold pressor test in haplotype 4 with the other haplotype families. If there are no differences among haplotypes, then the haplotypes will be combined to analyze.

Recruitment & Eligibility

Inclusion Criteria

Men and women aged 18 - 45 years inclusive.
Women of the above age will be studied between day 1 and day 14 of a normal menstrual cycle.
Subjects must be willing to give informed consent for the study and able to adhere to the study diet and study procedures.
Subjects and immediate extended family up till grandparents will be Caucasians or African Americans only.
Subjects will be free of any clinically significant disease.
Clinical laboratory test (CBC, blood chemistry) will be within acceptable limits.

Exclusion Criteria

Subjects who have taken any antiplatelet, anticoagulant or procoagulant medicines within the last three weeks preceding the study.
Subjects who have taken medications (including over the counter medications) other than oral contraceptives in the past two weeks.
Subjects who smoke or have smoked in the past 3 months.
Subjects who are presently or were formerly a narcotic addict or alcoholic.
Females with a positive pregnancy test.
Females who are breast feeding.

Primary Outcome Measures

Name	Time	Method
LogEC50 Platelet Aggregation	at 6am and 930am	EC50 represents the epinephrine concentration that produced 50% of maximal platelet aggregation (representing sensitivity to epinephrine) EC50 values were not normally distributed and were log-transformed for analyses.

Secondary Outcome Measures

Name	Time	Method
Percentage, Adenosine Diphosphate (ADP) Induced Platelet Aggregation	at 6am and 930am	Blood samples were taken from participants and centrifuged. Adenosine Diphosphate (ADP) at a fixed concentration of 2.5 uM was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation.
Percentage, Collagen Induced Platelet Aggregation	at 6am and 930am	Blood samples were taken from participants and centrifuged. Collagen at a fixed concentration of 2.5 ug/ml was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation.