Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants

Objective: The objective of the study was to study the genetic risk factors of spontaneous preterm birth (PTB) in African Americans. Study Design: Case-control analyses were performed using maternal and fetal deoxyribonucleic acid from 279 African American birth events (82 PTB and 197 term) and 1432 single-nucleotide polymorphisms from 130 candidate genes. Single-locus association and haplotype analyses were performed. Results: The most significant associations were in the maternal interleukin (IL)-15 (rs10833, allele P = 2.91 × 10^-4, genotype P = 2.00 × 10^-3) gene and the fetal IL-2 receptor B (IL-2RB) (rs84460, allele P = 1.37 × 10^-4, genotype P = 6.29 × 10^-4) gene. The best models for these markers were additive (rs10833, odds ratio [OR], 0.30; 95% confidence interval [CI], 0.14-0.62; P = 1.0 × 10^-3; rs84460, OR, 2.32; 95% CI, 1.47-3.67; P < 1.0 × 10^-3). The largest number of significant associations was found in genes related to infection and inflammation. There were overall a larger number of significant associations in infants than in mothers. Conclusion: These results support a strong role for genes involved in infection and inflammation in the pathogenesis of PTB, particularly IL-12 and IL-12RB, and indicate that in African Americans there may be complementarity of maternal and fetal genetic risks for PTB.