Despite years of intense efforts to reduce the rates of preterm birth (PTB), our understanding of the underlying mechanisms of PTB and racial disparity is limited. Recent data suggests that infection/inflammation has an important, complex role in early PTB. However, the mechanisms that modulate its clinical expression remain poorly understood. There is compelling evidence that PTB is a heterogenous complex entity determined by multiple genetic environmental factors. Studies by our team have demonstrated strong evidence of gene-environment interaction PTB in both Chinese and U.S. populations. This proposed study is to investigate the role of infection/inflammation genetic susceptibility, and gene-environment interactions in determining preterm disparities among three racial groups (Black, White, and Hispanic) in the U.S. We hypothesize that the risk of PTB associated with infection/inflammation is elevated in individuals with the relevant variants of candidate genes: 1) those involved in the initiation and regulation infectious/inflammatory process: Interleukin 1 (IL-l), IL-6, IL-l0, and tumor necrosis factor (TNF); 2) those involved more distally in the cascade of inflammatory process that lead to PTB: corticotropin releasing hormone (CRH); 3) those that may modify infectious/inflammatory process: C-reactive protein (CRP) and protein C. We further hypothesize that the significant racial disparity in PTB may be partially explained by: 1) differences in allele frequencies of the above candidate genes; 2) differences in the prevalence of intrauterine infection/inflammation; and 3) differences in gene-infection and gene-environment interactions. We will utilize the existent epidemiologic and clinical data biospecimens from a total of 1,000 preterm mother-infant pairs (cases) and 2,000 term controls being collected at Boston Medical Center. This proposal seeks support to accomplish two new specific aims: (1) to genotype the above proposed candidate genes for all the mothers and their infants in the study; and (2) to perform statistical analyses to test the above hypotheses. We have assembled a multi-disciplinary team that possesses technical and intellectual capability and relevant experience to carry out the study. Another important strength of this proposal is the existent large multi racial U.S. samples. The findings from this proposed study will expand our understanding of the role of infection/inflammation, genetic susceptibility , and gene-environment interactions in the pathogenesis of PTB in determining racial disparities in PTB.
Showing the most recent 10 out of 69 publications
