Atherosclerosis 137 (1998) 187 – 195 Racial differences in the distribution of a low density lipoprotein receptor-related protein (LRP) polymorphism and its association with serum lipoprotein, lipid and apolipoprotein levels Meagan R. Harris a , Clareann H. Bunker b , Richard F. Hamman c , Dharambir K. Sanghera a , Christopher E. Aston a , M. Ilyas Kamboh a, * a Department of Human Genetics, Graduate School of Public Health, Uniersity of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA b Department of Epidemiology, Graduate School of Public Health, Uniersity of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA 15261, USA c Department of Preentie Medicine and Biometrics, Uniersity of Colorado Health Science Center, Dener, CO 80262, USA Received 10 October 1996; received in revised form 18 February 1997; accepted 8 July 1997 Abstract The low density lipoprotein (LDL) receptor-related protein (LRP) is a cell receptor that has close structural homology to the LDL and very low density lipoprotein receptors and thus is believed to play an important role in lipid metabolism. This study was carried out to evaluate the distribution of a known tetranucleotide repeat polymorphism in the LRP gene and its association with serum lipoprotein-lipid and apolipoprotein levels in four large samples comprising Hispanics (n =373) and non-Hispanic Whites (n =522) from the U.S. and Nigerian Blacks from Sokoto (n =390) and Benin (n =800). A total of four alleles, designated 83, 87, 91 and 95 bp, were observed. The 83 bp allele was observed at 0.4–1.1% in the two U.S. populations but was completely absent in African Blacks. Sokoto Blacks had significantly different frequencies of the 87 and 91 bp alleles compared to Hispanics (P =0.008) and non-Hispanic Whites (P =0.024). The frequency of the 91 bp allele was also significantly higher in Benin Blacks compared to Hispanics (P =0.026) and non-Hispanic Whites (P =0.054). The analysis of the relationship between the LRP polymorphism and serum lipid traits yielded some significant race and gender specific significant association for lipoprotein(a) in non-Hispanic White males (P =0.02); HDL 2 -cholesterol in Hispanic females (P =0.03) and apolipoprotein B in Benin males (P =0.04). We also observed an interaction between the LRP polymorphism and menopausal status for Lp(a) in Hispanic famales (P =0.014). However, considering multiple comparisons were performed, these associations could be due to chance. Our data indicate that although the LRP tetranucleotide polymorphism exhibits inter-racial differences in its distribution, it does not appear to have a significant role in affecting serum lipid traits. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: LRP; Polymorphism; Lipoprotein-lipids; Apolipoproteins; Blacks; Hispanics; Non-Hispanic whites 1. Introduction The low density lipoprotein (LDL) receptor-related protein (LRP) is an endocytic receptor that binds many different ligands including, among others, apolipo- protein (apo) E, apo E containing chylomicron rem- nants,  2MR2-macroglobulin ( 2MR), vitellogenin, the receptor associated protein, tissue-type plasminogen ac- tivator and urokinase-type plasminogen activator [1 – 5]. The structure of LRP was first described by Herz et al. [6] which later on was found to be identical to the structure of the  2MR and hence led to the name  2MR/LRP [2]. The human LRP gene is localized to chromosome 12q13-14 [7], covers 90 kb of genomic DNA and contains 89 exons which code for a 15 kb mRNA [8]. LRP is synthesized as a single-chain precur- sor that is cleaved in the trans golgi to a 515 kDa heavy * Corresponding author. Tel.: +1 412 6243066; fax: +1 412 3837844; e-mail: IKamboh@helix.hgen.pitt.edu 0021-9150/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0021-9150(97)00230-X