Prospective analysis of mannose-binding lectin genotypes and coronary artery disease in American Indians: the Strong Heart Study.
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.


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.
Best
Lyle G
LG
Missouri Breaks Industries Research Inc, Timber Lake, SD, USA. sbest@utma.com
Davidson
Michael
M
North
Kari E
KE
MacCluer
Jean W
JW
Zhang
Ying
Y
Lee
Elisa T
ET
Howard
Barbara V
BV
DeCroo
Susan
S
Ferrell
Robert E
RE
D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D007198:Indians, North American / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D011446:Prospective Studies
D037601:Mannose-Binding Lectin