Polymorphisms in inflammatory genes are associated with term small for gestational age and preeclampsia.
OBJECTIVE
Inflammatory biomarkers are associated with preeclampsia (PE) and poor fetal growth; however, genetic epidemiologic studies have been limited by reduced gene coverage and the exclusion of African American mothers.


METHODS
Cases and controls (N = 1646) from a pregnancy cohort were genotyped for 503 tagSNPs in 40 genes related to inflammation. Gene-set analyses were stratified by race and were followed by a single SNP analysis within significant gene sets.


RESULTS
Gene-level associations were found for IL6 and KLRD1 for term small for gestational age (SGA) among African Americans. LTA/TNF and TBX21 were associated with PE among European Americans. The strongest association was for PE among European Americans for an upstream regulator of TNF with RR = 1.8 (95% CI 1.1-2.7).


CONCLUSIONS
Although previous studies have suggested null associations, increased tagging and stratification by genetic ancestry suggests important associations between IL6 and term SGA for African Americans, and a TNF regulator and PE among European Americans (N = 149).
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Quaker E
QE
Harmon
Stephanie M
SM
Engel
Michael C
MC
Wu
Thomas M
TM
Moran
Jingchun
J
Luo
Alison M
AM
Stuebe
Christy L
CL
Avery
Andrew F
AF
Olshan
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology; D000328:Adult; D001741:Black or African American; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D007249:Inflammation / Q000208:ethnology / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000208:ethnology* / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D014481:United States / Q000453:epidemiology; D044465:White People; D000098815:T-bet Transcription Factor
D048868:Adaptor Proteins, Signal Transducing; C508600:IL6 protein, human; D015850:Interleukin-6; C497869:KLRD1 protein, human; D008233:Lymphotoxin-alpha; D051920:NK Cell Lectin-Like Receptor Subfamily D; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C524349:TBKBP1 protein, human
African Americans; genetic association studies; preeclampsia; pregnancy; small for gestational age