Published Online
on January 19, 2004

A more recent version of this article appeared on February 3, 2004

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Submitted on June 16, 2003
Revised on September 18, 2003
Accepted on October 23, 2003

Prospective Analysis of Mannose-Binding Lectin Genotypes and Coronary Artery Disease in American Indians. The Strong Heart Study

Lyle G. Best MD^*, Michael Davidson MD, MPH, PhD, Kari E. North PhD, Jean W. MacCluer PhD, Ying Zhang PhD, Elisa T. Lee PhD, Barbara V. Howard PhD, Susan DeCroo MS, and Robert E. Ferrell PhD

From Missouri Breaks Industries Research Inc (L.G.B.), Timber Lake, SD; Medstar Research Institute (M.D., B.V.H.), Washington, DC; University of North Carolina (K.E.N.), Chapel Hill, NC; Southwest Foundation for Biomedical Research (J.W.M.), San Antonio, Tex; University of Oklahoma Health Sciences Center (Y.Z., E.T.L.), Oklahoma City, Okla; and University of Pittsburgh (S.D., R.E.F.), Pittsburgh, Pa.

^* To whom correspondence should be addressed. E-mail: sbest{at}utma.com.

Background--Mannose-binding lectin (MBL) is a circulating immune factor responsible for opsonization of pathogens and directly activating complement. Common variations in the MBL gene are responsible for an opsonic deficiency that affects 5% to 7% of whites and are associated with increased susceptibility to infections. After a preliminary report associating these variations with coronary artery disease (CAD), we determined MBL genotypes in 3 American Indian communities experiencing an increased mortality and morbidity from CAD.

Methods and Results--We examined DNA from 434 participants in a population-based cohort, the Strong Heart Study. Genotypes for 3 common MBL coding variations and 1 promoter polymorphism were determined. The frequency of a composite genotype that conferred low MBL levels was 20.7% in 217 cases and 11.1% in matched controls without CAD. A conditional logistic regression model indicated a univariate OR for CAD of 2.3 (95% CI 1.3 to 4.2, P=0.005) for the variant genotypes. After adjustment for demographic and CAD risk factors, including type 2 diabetes mellitus, fibrinogen, triglycerides, and hypertension, the OR was 3.2 (95% CI 1.5 to 7.0, P=0.004).

Conclusions--Variant MBL genotypes coding for markedly diminished levels of MBL are predictive of CAD. After adjustment for multiple traditional risk factors for ischemic heart disease, this association remains significant. A high prevalence of variant MBL alleles and CAD in this population suggests that potentially important public health benefits may accrue from future interventions based on these genotypes.

Key words: coronary disease • genetics • inflammation • immune system • epidemiology

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