Transmission of parentally shared human leukocyte antigen alleles and the risk of preterm delivery

OBJECTIVE: Our objective was to examine our hypothesis that the transmission of parentally shared human leukocyte antigen (HLA) alleles to offspring increases the risk of preterm delivery. METHODS: A population-based family study with participating children and their parents was conducted in Kaiser Permanente Medical Care Program, an integrated healthcare delivery system, in the Northern California Region. A total of 234 participants from 78 families with early preterm deliveries (35 weeks of gestation or greater) and 60 participants from 20 families with full-term births were included in the study. Buccal cells were collected from the first-born preterm cases and their parents to determine HLA-B (class I) and DRB1 (class II) types and the transmission of parental alleles to the offspring. The buccal samples were also collected from full-term deliveries to rule out possible segregation distortion at the studied HLA loci. RESULTS: Compared with the expected transmission probability based on Mendel's laws (25%), transmission of parentally shared HLA-B or DRB1 alleles from both heterozygous parents to offspring (48% of 23 heterozygous parents) was associated with a more than 5-fold increased risk of preterm delivery (odds ratio 5.5; 95% confidence interval 1.2-51). Transmission of parentally shared HLA alleles from heterozygous mothers (83%) appears to be more important in the etiology of preterm delivery than transmission from fathers (57%). The transmission pattern of parentally shared HLA alleles in our full-term controls was almost identical to the expected pattern based on Mendel's laws and demonstrated no segregation distortion at those HLA loci. CONCLUSION: Our findings provide evidence that the transmission of parentally shared HLA alleles may be an underlying mechanism for preterm delivery.