1. ¹Department of Psychiatry, UC San Diego, La Jolla, CA, USA
2. ²Wilson Research and Consulting, LLC, Cincinnati, OH, USA
3. ³University of the West Indies, Barbados
4. ⁴University of the West Indies, EC
5. ⁵Director of Primary Care, Ministry of Health, Dominica
6. ⁶Share Care Research and Education, Inc., Milwaukee, WI, USA
7. ⁷Department of Internal Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

Correspondence: Dr CE Grim, Shared Care Research, Education and Consulting, Inc., 2821 N 4th St., Suite 410, Milwaukee, WI 53211, USA. E-mail: lowerbp2@aol.com

Received 3 April 2003; Revised 5 November 2003; Accepted 24 November 2003; Published online 12 February 2004.

Abstract

Population blood pressure variation is most likely due to multiple genes. This is likely the reason why monogenic testing with the angiotensinogen (AGT) gene polymorphisms on chromosome 1 (1q42–43), especially M235T, has met with negative results, especially in those of African descent. The RH blood group system, also on chromosome 1 (1 p36.2–34), has likewise been associated with blood pressure variation in African-Americans and with the rise in blood pressure with age in whites. Using a random sample of the population, we investigated the combined effects of single and combined variation of the AGTN M235T and RH genotypes on blood pressure, lipids, and lipoprotein concentrations in Afro-Caribbeans aged 18–60 years from the island nation of Dominica. In monogenic analysis, AGT M235T was not associated with blood pressure. However, it was associated with HDL (MM 4223, MT 4412, TT 5214 (P=0.002)). RH genotype was significantly associated with systolic blood pressure (P=0.006) and Apo-A (P=0.003). These effects remained after adjustment for age, gender, weight, and BMI. In the polygenetic analysis, AGT M235T and RH were significantly associated with systolic blood pressure (P=0.037; interaction effects, P=0.068). The association of the AGT M235T with blood pressure across RH blood group haplotypes was then tested. Of the five RH haplotypes available for analysis, the AGT M235T was significantly associated with blood pressure within the "D" haplotype (P=0.01). The RH blood group and gender were significantly associated with systolic blood pressure and Apo-A levels (P=0.005 and 0.012, respectively). All interactions were independent of age and weight. In conclusion, we demonstrate a significant association of AGT M235T with blood pressure and cholesterol metabolism in an Afro-Caribbean population in the "genetic context" of the RH blood group system. Further investigation of these interactions may help understand the effects of genetic factors on cardiovascular risk in African-derived and other populations.