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Articles by K. L Lunetta
Total Records ( 1 ) for K. L Lunetta
  R. B Schnabel , K. L Lunetta , M. G Larson , J Dupuis , I Lipinska , J Rong , M. H Chen , Z Zhao , J. F Yamamoto , J. B Meigs , V Nicaud , C Perret , T Zeller , S Blankenberg , L Tiret , J. F Keaney , R. S Vasan and E. J. Benjamin
 

Background— Environmental and genetic correlates of inflammatory marker variability are incompletely understood. In the family-based Framingham Heart Study, we investigated heritability and candidate gene associations of systemic inflammatory biomarkers.

Methods and Results— In offspring participants (n=3710), we examined 11 inflammatory biomarkers (CD40 ligand, C-reactive protein, intercellular adhesion molecule-1, interleukin-6, urinary isoprostanes, monocyte chemoattractant protein-1, myeloperoxidase, P-selectin, tumor necrosis factor-, tumor necrosis factor receptor II, fibrinogen). Heritability and bivariate genetic and environmental correlations were assessed by Sequential Oligogenic Linkage Analysis routines in 1012 family members. We examined 1943 tagging single-nucleotide polymorphisms in 233 inflammatory pathway genes with ≥5 minor allele carriers using a general genetic linear model. Clinical correlates explained 2.4% (CD40 ligand) to 28.5% (C-reactive protein) of the variability in inflammatory biomarkers. Estimated heritability ranged from 10.9% (isoprostanes) to 44.8% (P-selectin). Most correlations between biomarkers were weak although statistically significant. A total of 45 single-nucleotide polymorphism-biomarker associations met the q-value threshold of 0.25. Novel top single-nucleotide polymorphisms were observed in ICAM1 gene in relation to intercellular adhesion molecule-1 concentrations (rs1799969, P=1.32x10–8) and MPO in relation to myeloperoxidase (rs28730837, P=1.9x10–5). Lowest P values for trans-acting single-nucleotide polymorphisms were observed for APCS with monocyte chemoattractant protein-1 concentrations (rs1374486, P=1.01x10–7) and confirmed for IL6R with interleukin-6 concentrations (rs8192284, P=3.36x10–5). Novel potential candidates (APCS, MPO) need to be replicated.

Conclusions— Our community-based data support the relevance of clinical and genetic factors for explaining variation in inflammatory biomarker traits.

 
 
 
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