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Several epidemiological studies have established that elevated serum lipoprotein (a) [Lp(a)] levels are independent risk factors for coronary heart disease, stroke, and restenosis of coronary lesions in white and Asian populations. Serum Lp(a) levels vary over a 1000-fold range among individuals and are under strict genetic control. Serum Lp(a) levels are significantly higher in populations with African ancestry than in populations of European ancestry. The APOA gene exhibits hypervariable length polymorphism resulting from a variable number of expressed kringle 4 repeats. An inverse relationship exists between the size of kringle 4 repeats and serum Lp(a) levels. However, most studies have been conducted in whites, and the data are scanty in African populations. To explore this relationship among Africans, we determined serum Lp(a) levels and APOA Kringle 4 size polymorphisms in 781 unrelated Africans (490 men, 291 women) from Benin City, Nigeria. Mean and median serum Lp(a) values were 25.6 ± 0.6 mg/dl and 20.9 mg/dl, respectively. Although there was no difference in mean Lp(a) values between men and women, median Lp(a) values were higher in women than in men (p = 0.02). Using SDS-agarose gel electrophoresis, we detected 38 APOA isoforms, the highest number recorded to date. There were 10 consecutive medium-size alleles whose frequencies ranged between 4.2% and 10.9%, and together they accounted for 72.8% of the alleles observed in this population. Spearman’s correlation coefficients showed an inverse relationship between the size of the APOA isoform and Lp(a) levels using either single-banded (r = 0.46; p < 0.0001) or double-banded (r = 0.42; p < 0.0001) phenotypes. Using random effects analysis of variance on the entire sample, the APOA size polymorphism explained about 15% of the phenotypic variation in Lp(a) levels. These data suggest that despite significant correlation between the APOA kringle 4 size polymorphism and Lp(a) levels, other sequence variations either in the APOA gene or closely linked genes may account for relatively higher Lp(a) levels found in Africans.