Table 3 Disease functions as detected by IPA based on significant genetic variations in maternal and fetal candidate genes in African Americans and its interpretation in spontaneous preterm birth.

Inflammatory disease

ACE, CCL2, CTLA4, IFNG, IL4, IL15, IL10RA, IL1B, IL1R1, IL2RA, IL2RB, IL4R, IL6R, KL, MMP2, MMP8, NFKB1, NOD2, NR3C1, POMC, PTGER3, SLC6A4, TIMP3, TNFR1, TNFR2, VEGFA

CD14, CTLA4, IFNG, IL2, IL6, IL8, IL10, IL15, IL10RB, IL1R1, IL1RN, IL2RB, MMP2, MMP3, MMP8, MMP9, NFKB1, NFKBIB, NOD2, PTGER3, TIMP3, TLR4, TNF, TNFR1, TNFR2, TREM1

Overwhelming inflammation appears to be the primary effecter of preterm birth in African Americans regardless of etiology. Fetal response is dominant (see Figure 2) along with complementary maternal contributions. This combined inflammatory process that can activate multitudes of other pathways seem primary disease function resulting in preterm birth

Etiology → Inflammation → Activation of multitudes of uterotonic events → Preterm birth

Connective tissue disease

CCL2, IFNG, IL4, IL15, IL10RA, IL1B, IL1R1, IL2RB, IL4R, IL6R, MMP2, NFKB1, NR3C1, POMC, SLC6A4, TIMP3, TNFR1, NFR2,

IFNG, IL6, IL8, IL10, IL15, IL1R1, IL1RN, IL2RB, MMP2, MMP3, MMP9, NFKB1, TIMP3, TLR4, TNF, TNFR1, TNFR2

This function also involves immune and inflammatory response genes. Matrix metalloproteinases can function in inflammation as well as collagen turnover function; e.g. involved in cervical ripening and membrane matrix degradation.

Skeletal and muscular disorder

CCL2, CTLA4, IFNG, IL4, IL15, IL10RA, IL1B, IL1R1, IL2RB, IL4R, IL6R, KL, MMP2, NFKB1, NOD2, NR3C1, POMC, SLC6A4, TNFR1, TNFR2, VEGFA

CD14, CTLA4, IFNG, IL2, IL6, IL8, IL10, IL15, IL1R1, IL1RN, IL2RB, MMP2, MMP3, MMP9, NFKB1, NFKBIB, NOD2, TLR4, TNF, TNFR1, TNFR2, TSHR

Most of these genes function in inflammatory regulation are related to rheumatic disorders, including matrix metalloproteinases that are also involved in cervical ripening and membrane matrix degradation.