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(Circulation. 2004;109:471-475.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

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; 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.

Reprint requests to Lyle Best, MD, #1 Airport Rd, RR1, Box 88, Rolette, ND 58366. E-mail sbest{at}utma.com

Received June 16, 2003; de novo received September 18, 2003; accepted October 23, 2003.

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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