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We hypothesized that apolipoprotein-E (apo-E) genotypes would be associated with plasma lipid indices in newborns of South Asian (SA) ancestry but not in newborns of African (Afr) ancestry. Cord blood was obtained by consecutive sampling at maternity hospitals in the Caribbean Islands of Trinidad and Curaçao. Apolipoprotein-E genotypes, cholesterol, triglycerides, apo-A, apo-B and Lipoprotein (a) (Lp(a)) were measured in 294 newborns in Trinidad and 234 in Curaçao. The apo-B/apo-AI ratio and an adapted lipid tetrad index (i.e. cholesterol x triglycerides x Lp(a)/apo-AI) were calculated. In Trinidad, apo-E allele frequencies and genotype distributions of Afr and SA were significantly (p < 0.001) different (Afr: n = 71: apo-e2 : e3 : e4 = 10.4 : 66.4 : 23.2%; SA: n = 98; e2 : e3 : e4 = 3.5 : 83.1: 13.4%). The Mixed group (SA + Afr) had apo-E allele frequencies in between those of SA and Afr groups (n = 115; e2 : e3 : e4 = 7 : 76 : 17%). Lipid indices of appropriate for gestational age and term newborns were comparable, except for lower Lp(a) (SA = 29+/-4; Afr = 46+/-5; Mixed = 41+/-5 mg L(-1)) and lower adapted lipid tetrad index (29.4+/-4.8; 41.9+/-5.4; 41.4+/-7.0) in SA. Apo-E allele frequencies of Curaçao newborns were: apo-e2 : e3 : e4 = 10.5 : 72.6 : 16.9%. Their Lp(a) levels were significantly higher (68+/-3 mg L(-1)) than that of the Trinidadian sample (38+/-3; p < 0.0001). Apolipoprotein-E4 had an apo-B-increasing effect and apo-E2 an apo-B-decreasing effect in Afr (r = 0.192, p = 0.003). Among Africans from Trinidad and Curaçao variations in apo-E4 and apo-E2 are associated with an apo-B-increasing effect and an apo-B-decreasing effect, respectively. There was no relationship between apo-E polymorphism and lipids among South Asians.