Skip NavigationSkip to Content
Return Return to Search Results

Three single-nucleotide polymorphisms in LPA account for most of the increase in lipoprotein(a) level elevation in African Americans compared with European Americans

  1. Author:
    Chretien, J. P.
    Coresh, J.
    Berthier-Schaad, Y.
    Kao, W. H. L.
    Fink, N. E.
    Klag, M. J.
    Marcovina, S. M.
    Giaculli, F.
    Smith, M. W.

  2. Author Address

    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Washington, Dept Med, NW Lipid Res Labs, Seattle, WA 98195 USA. NCI, Lab Gen Divers, Frederick, MD 21701 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21701 USA.;Coresh, J, Johns Hopkins Univ, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA.;coresh@jhu.edu
    1. Year: 2006
    2. Date: Dec
  2. Journal: Journal of Medical Genetics
    1. 43
    2. 12
    3. Pages: 917-923
  4. Type of Article: Article
  5. ISSN: 0022-2593
  1. Abstract:

    Background: The extent which universally common or population-specific alleles can explain between-population variations in phenotypes is unknown. The heritable coronary heart disease risk factor lipoprotein(a) (Lp(a)) level provides a useful case study of between-population variation, as the aetiology of twofold higher Lp(a) levels in African populations compared with non-African populations is unknown. Objective: To evaluate the association between LPA sequence variations and Lp(a) in European Americans and African Americans and to determine the extent to which LPA sequence variations can account for between-population variations in Lp(a). Methods: Serum Lp(a) and isoform measurements were examined in 534 European Americans and 249 African Americans from the Choices for Healthy Outcomes in Caring for End-Stage Renal Disease Study. In addition, 12 LPA variants were genotyped, including 8 previously reported LPA variants with a frequency of > 2% in European Americans or African Americans, and four new variants. Results: Isoform-adjusted Lp(a) level was 2.23-fold higher among African Americans. Three single-nucleotide polymorphisms (SNPs) were independently associated with Lp(a) level (p < 0.02 in both populations). The Lp(a)-increasing SNP (G-21A, which increases promoter activity) was more common in African Americans, whereas the Lp(a)-lowering SNPs (T3888P and G+1/inKIV-8A, which inhibit Lp(a) assembly) were more common in European Americans, but all had a frequency of < 20% in one or both populations. Together, they reduced the isoform-adjusted African American Lp(a) increase from 2.23 to 1.37-fold(a 60% reduction) and the between-population Lp(a) variance from 5.5% to 0.5%. Conclusions: Multiple low-prevalence alleles in LPA can account for the large between-population difference in serum Lp(a) levels between European Americans and African Americans.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1136/jmg.2006.042119
  3. View record in Web of Science®
  4. WOS: 000242483900004

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel