The association of mannose binding lectin genotype and immune response to Chlamydia pneumoniae: The Strong Heart Study.
The association of mannose binding lectin genotype and immune response to Chlamydia pneumoniae: The Strong Heart Study.
- 2019
Available online through MWHC library: 2006 - present
Cardiovascular disease (CVD) is an important contributor to morbidity and mortality in American Indian communities. The Strong Heart Study (SHS) was initiated in response to the need for population based estimates of cardiovascular disease in American Indians. Previous studies within SHS have identified correlations between heart disease and deficiencies in mannose binding lectin (MBL), a motif recognition molecule of the innate immune system. MBL mediates the immune response to invading pathogens including Chlamydia pneumoniae (Cp), which has also been associated with the development and progression of CVD. However, a link between MBL2 genotype and Cp in contributing to heart disease has not been established. To address this, SHS collected baseline Cp antibody titers (IgA and IgG) and MBL2 genotypes for common functional variants from 553 individuals among twelve participating tribes. A single nucleotide polymorphism (SNP) in the promoter, designated X/Y, correlated significantly with increased Cp IgG titer levels, whereas another promoter SNP (H/L) did not significantly influence antibody levels to Cp. Two variants within exon 1 of MBL2, the A and B alleles, also displayed significant association with Cp antibody titers. Some MBL2 genotypes were absent from the population, suggesting linkage disequilibrium may be operating within the SHS cohort. Additional factors, such as increasing age and socioeconomic status, were also associated with increased Cp IgG antibody titers. This study demonstrates that MBL2 genotype associates with immune reactivity to C. pneumoniae in the SHS cohort. Thus, MBL2 may contribute to the progression of cardiovascular disease (CVD) among American Indians indirectly through pathogen interactions in addition to its previously defined roles.
English
1932-6203
10.1371/journal.pone.0210640 [doi] PONE-D-18-14165 [pii]
*Chlamydophila pneumoniae/me [Metabolism]
*Chlamydophila pneumoniae/py [Pathogenicity]
*Mannose-Binding Lectin/me [Metabolism]
Aged
Alleles
Cardiovascular Diseases/ge [Genetics]
Cardiovascular Diseases/me [Metabolism]
Cardiovascular Diseases/pa [Pathology]
Case-Control Studies
Chlamydophila pneumoniae/ge [Genetics]
Female
Genetic Predisposition to Disease/ge [Genetics]
Genotype
Humans
Indians, North American
Linkage Disequilibrium/ge [Genetics]
Male
Mannose-Binding Lectin/ge [Genetics]
Middle Aged
Polymorphism, Single Nucleotide/ge [Genetics]
Promoter Regions, Genetic/ge [Genetics]
MedStar Health Research Institute
Journal Article
Available online through MWHC library: 2006 - present
Cardiovascular disease (CVD) is an important contributor to morbidity and mortality in American Indian communities. The Strong Heart Study (SHS) was initiated in response to the need for population based estimates of cardiovascular disease in American Indians. Previous studies within SHS have identified correlations between heart disease and deficiencies in mannose binding lectin (MBL), a motif recognition molecule of the innate immune system. MBL mediates the immune response to invading pathogens including Chlamydia pneumoniae (Cp), which has also been associated with the development and progression of CVD. However, a link between MBL2 genotype and Cp in contributing to heart disease has not been established. To address this, SHS collected baseline Cp antibody titers (IgA and IgG) and MBL2 genotypes for common functional variants from 553 individuals among twelve participating tribes. A single nucleotide polymorphism (SNP) in the promoter, designated X/Y, correlated significantly with increased Cp IgG titer levels, whereas another promoter SNP (H/L) did not significantly influence antibody levels to Cp. Two variants within exon 1 of MBL2, the A and B alleles, also displayed significant association with Cp antibody titers. Some MBL2 genotypes were absent from the population, suggesting linkage disequilibrium may be operating within the SHS cohort. Additional factors, such as increasing age and socioeconomic status, were also associated with increased Cp IgG antibody titers. This study demonstrates that MBL2 genotype associates with immune reactivity to C. pneumoniae in the SHS cohort. Thus, MBL2 may contribute to the progression of cardiovascular disease (CVD) among American Indians indirectly through pathogen interactions in addition to its previously defined roles.
English
1932-6203
10.1371/journal.pone.0210640 [doi] PONE-D-18-14165 [pii]
*Chlamydophila pneumoniae/me [Metabolism]
*Chlamydophila pneumoniae/py [Pathogenicity]
*Mannose-Binding Lectin/me [Metabolism]
Aged
Alleles
Cardiovascular Diseases/ge [Genetics]
Cardiovascular Diseases/me [Metabolism]
Cardiovascular Diseases/pa [Pathology]
Case-Control Studies
Chlamydophila pneumoniae/ge [Genetics]
Female
Genetic Predisposition to Disease/ge [Genetics]
Genotype
Humans
Indians, North American
Linkage Disequilibrium/ge [Genetics]
Male
Mannose-Binding Lectin/ge [Genetics]
Middle Aged
Polymorphism, Single Nucleotide/ge [Genetics]
Promoter Regions, Genetic/ge [Genetics]
MedStar Health Research Institute
Journal Article