Genetic linkage of serum homocysteine in dominican families: The family study of stroke risk and carotid atherosclerosis

David Della Morte, Ashley Beecham, Tatjana Rundek, Susan Slifer, Bernadette Boden-Albala, Mark S. McClendon, Susan H Blanton, Ralph L Sacco

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background and purpose: Homocysteine levels are determined by genetic and environmental factors. Several studies have linked high plasma levels of total homocysteine to the increased risk of cardiovascular disease, stroke, and many other conditions. However, the exact mechanism of documented and novel total homocysteine quantitative trait loci to that risk is unknown. Methods: We have performed linkage analysis in 100 high-risk Dominican families with 1362 members. Probands were selected from the population-based Northern Manhattan Study. A set of 405 microsatellite markers was used to screen the whole genome. Variance components analysis was used to detect evidence for linkage after adjusting for stroke risk factors. Ordered-subset analysis based on Dominican Republic enrollment was conducted. Results: Total homocysteine levels had a heritability of 0.44 (P<0.0001). The most significant evidence for linkage was found at chromosome 17q24 (maximum logarithm of odds [MLOD]=2.66, P=0.0005) with a peak at D17S2193 and was significantly increased in a subset of families with a high proportion of Dominican Republic enrollment (MLOD=3.92, P=0.0022). Additionally, modest evidence for linkage was found at chromosome 2p21 (MLOD=1.77, P=0.0033) with a peak at D2S1356 and was significantly increased in a subset of families with a low proportion of Dominican Republic enrollment (MLOD=2.82, P=0.0097). Conclusions: We found a strong evidence for novel quantitative trait loci on chromosomes 2 and 17 for total homocysteine plasma levels in Dominican families. Our family study provides essential data for a better understanding of the genetic mechanisms associated with elevated total homocysteine levels leading to cardiovascular disease after accounting for environmental risk factors.

Original languageEnglish
Pages (from-to)1356-1362
Number of pages7
JournalStroke
Volume41
Issue number7
DOIs
StatePublished - Jul 1 2010

Fingerprint

Carotid Artery Diseases
Genetic Linkage
Homocysteine
Stroke
Dominican Republic
Serum
Quantitative Trait Loci
Cardiovascular Diseases
Chromosomes
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 2
Microsatellite Repeats
Analysis of Variance
Myocardial Infarction
Genome
Population

Keywords

  • cardiovascular disease
  • Dominican families
  • genetic linkage
  • homocysteine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Genetic linkage of serum homocysteine in dominican families : The family study of stroke risk and carotid atherosclerosis. / Della Morte, David; Beecham, Ashley; Rundek, Tatjana; Slifer, Susan; Boden-Albala, Bernadette; McClendon, Mark S.; Blanton, Susan H; Sacco, Ralph L.

In: Stroke, Vol. 41, No. 7, 01.07.2010, p. 1356-1362.

Research output: Contribution to journalArticle

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AU - Della Morte, David

AU - Beecham, Ashley

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AU - Slifer, Susan

AU - Boden-Albala, Bernadette

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