Genetic and other factors determining mannose-binding lectin levels in American Indians: the Strong Heart Study.
BACKGROUND
Mannose-binding lectin (MBL) forms an integral part of the innate immune system. Persistent, subclinical infections and chronic inflammatory states are hypothesized to contribute to the pathogenesis of atherosclerosis. MBL gene (MBL2) variants with between 12 to 25% allele frequency in Caucasian and other populations, result in markedly reduced expression of functional protein. Prospective epidemiologic studies, including a nested, case-control study from the present population, have demonstrated the ability of MBL2 genotypes to predict complications of atherosclerosis,. The genetic control of MBL2 expression is complex and genetic background effects in specific populations are largely unknown.


METHODS
The Strong Heart Study is a longitudinal, cohort study of cardiovascular disease among American Indians. A subset of individuals genotyped for the above mentioned case-control study were selected for analysis of circulating MBL levels by double sandwich ELISA method. Mean MBL levels were compared between genotypic groups and multivariate regression was used to determine other independent factors influencing MBL2 expression.


RESULTS
Our results confirm the effects of variant structural (B, C, and D) and promoter (H and Y) alleles that have been seen in other populations. In addition, MBL levels were found to be positively associated with male gender and hemoglobin A1c levels, but inversely related to triglyceride levels. Correlation was not found between MBL and other markers of inflammation.


CONCLUSIONS
New data is presented concerning the effects of known genetic variants on MBL levels in an American Indian population, as well as the relationship of MBL2 expression to clinical and environmental factors, including inflammatory markers.
Best
Lyle G
LG
Missouri Breaks Industries Research Inc, Timber Lake, SD, USA. sbest@utma.com
Ferrell
Robert E
RE
Decroo
Susan
S
North
Kari E
KE
Maccluer
Jean W
JW
Zhang
Ying
Y
Lee
Elisa T
ET
Howard
Barbara V
BV
Umans
Jason
J
Palmieri
Vittorio
V
Garred
Peter
P
D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D012044:Regression Analysis; D012307:Risk Factors
D037601:Mannose-Binding Lectin