Table 2 Disease functions as detected by IPA based on significant genetic variations in maternal and fetal candidate genes in Caucasians and its interpretation in spontaneous preterm birth.

Dermatologic disease and conditions

COL1A1, COL3A1, COL5A1, COL5A2, CTLA4, CYP19A1, IL5, IL10, IL18, MMP3, MMP1, NFKBIA, PLAT, PTGS1, TLR2, TLR7, TNFR1, TNFR2,

COL1A2, COL3A1, COL5A2, CYP19A1, IGF1, IL5, IL1A, IL1B, IL1RN, IL4R, MMP, NFKBIA, PGR, PTGS2, TLR7

Because dermatological disorders typically involve combined collagen remodeling aided by inflammation and, this function appears to reflect premature cervical ripening and membrane weakening related to preterm birth. Collagenolysis may involve an underlying inflammatory process as suggested by cytokines, cytokine receptors, cytokine signaling pathway genes that is likely a secondary event.

Etiology → Collagenolysis → inflammation → Premature cervical ripening and membrane weakening → Preterm birth.

Inflammatory disease

CCL2, CTLA4, CYP19A1, F7, IL5, IL10, IL18, IL1R1, MMP3, MMP1, NFKBIA, PLA2G4A, PLAT, PTGER3, PTGS1, TIMP3, TLR2, TNFR1, TNFR2

CRHR2, CYP19A1, IGF1, IL5, IL10RA, IL1A, IL1B, IL1RN, IL2RB, IL4R, KL, MMP8, MMP1, NFKBIA, PGR, PTGS2, TIMP3, TREM1

Underlying inflammatory conditions associated with preterm birth (see above)

Hematological disease

CCL2, CTLA4, CYP19A1, F5, F7, HSD11B1, IL5, IL10, IL18, IL1RAP, NFKBIA, PLA2G4A, PLAT, PTGS1, TLR2, TNFR1, TNFR2

CBS, IGF1, IL5, IL1A, IL1B, IL1RAP, IL1RN, IL2RB, IL4R, MMP8, NFKBIA, NFKBIE, PGR, PTGS2

Involvement of genes in the hematological pathway indicates decidual hemorrhage and associated problems associated with Caucasian preterm birth.