If we break down the process at the base of the mechanisms that, physiologically, regulate the normal duration of a pregnancy or, if altered, lead to the appearance of a preterm birth, we see that theoretically come into play such and many genetic factors that is impossible, at present, to understand and analyze them (47).

In fact, among these we remember:

a) The inflammatory pathway

b) The uterus and placental pathway

c) The endocrine pathway

d) The contractile mechanism pathway

e) The metabolic pathway

a) The inflammatory pathway

That includes about 80 proinflammatory factors that could, abstractly, once activated, enter the preterm birth mechanism and are encoded by specific genetic loci which, just as hypothetically, if they are altered can enter the mechanism of induction of a preterm birth or alteration of the duration of a gestation.

Colony-stimulating factor 1 CSF1 1p21-p13
Colony-stimulating factor 1 receptor CSF1R 5q33-q35
Colony-stimulating factor 2 CSF2 5q31.1
Colony-stimulating factor 2 receptor alpha CSF2RA Xp22.32 and Yp11.3
Colony-stimulating factor 2 receptor beta CSF2RB 22q13.1
Colony-stimulating factor 3 CSF3 17q11.2-q12
Colony-stimulating factor 3 receptor CSF3R 1p35-p34.3
Interferon gamma receptor 1 IFNGR1 6q23-q24
Interleukin-1α IL1A 2q14
Interleukin-1 receptor type I IL1R1 2q12
Interleukin-1 receptor type II IL1R2 2q12-q22
Interleukin-1 receptor antagonist IL1RN 2q14.2
Interleukin-1β IL1b 2q14
Interleukin-2 IL2 4q26-q27
Interleukin-2 receptor alpha IL2RA 10p15-p14
Interleukin-2 receptor beta IL2RB 22q13.1
Interleukin-4 IL4 5q31.1
Interleukin-4 receptor IL4R 16p11.2-12.1
Interleukin-5 IL5 5q31.1
Inteleukin-6 IL6 7p21
Interleukin-6 receptor IL6R 1q21
Interleukin-8 IL8 4q13-q21
Interleukin-8 receptor alpha IL8RA 2q35
Interleukin-10 IL10 1q31-q32
Interleukin-10 receptor alpha IL10RA 11q23
Interleukin-10 receptor beta IL10RB 21q22.11
Interleukin-11 IL11 19q13.3-q13.4
Interleukin-12A IL12A 3p12-q13.2
Interleukin-13 IL13 5q31
Interleukin-15 IL15 4q31
Interleukin-17 IL17 6p12
Interleukin-18 IL18 11q22.2-q22.3
Lymphotoxin alpha LTA 6p21.3
Lymphotoxin beta LTB 6p21.3
Nitric oxide synthase 2A NOS2A 17q11.2-q12
Nitric oxide synthase 3 NOS3 7q36
Tumor necrosis factor alpha TNFA 6p21.3
Type 1 tumor necrosis factor alpha receptor TNFR1 12p13.2
Type 2 tumor necrosis factor alpha receptor TNFR2 1p36.3-p36.2
Tumor necrosis factor receptor superfamily member 6 TNFRSF6 10q24.1
Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator ARTS-1 5q15
Gamma interferon IFN-? 12q14
Gamma interferon receptor 1 IFNGR1 6q23-q24
Neurotrophin-3 NT-3 12p13
Neurotrophin-5 NT-5 19q13.3
Triggering receptor expressed on myeloid cells 1 TREM-1 6p21.1
Migration inhibitory factor MIF 22q11.23
Pre-B-cell colony-enhancing factor 1 PBEF1 7q22.3
Nuclear factor kappa B NF-Kb 4q24
B-cell activating factor BAFF 13q32-34
Toll-like receptor 2 TLR2 4q32
Toll-like receptor 3 TLR3 4q35
Toll-like receptor 4 TLR4 9q32-q33
Toll-like receptor 5 TLR5 1q41-q42
Toll-like receptor 7 TLR7 Xp22.3
Toll-like receptor 8 TLR8 Xp22
Toll-like receptor 9 TLR9 3p21.3
CC chemokine receptor 5 CCR5 3p21
T-cell immunomodulatory protein CDA08 16q12.1
Monocyte chemoattractant protein 1 MCP-1 17q11.2-q12
Monocyte chemoattractant protein 2 MCP-2 17q11.2
Macrophage inflammatory protein-1α MIP-1a 17q11-q21
Macrophage inflammatory protein-1β MIP-1b 17q12
Intercellular adhesion molecule-1 ICAM-1 19p13.3-p13.2
Prolactin PRL 6p22.2-p21.3
Prolactin receptor PRLR 5p14-p13
Transforming growth factor β1 TGFB1 19q13.1
Transforming growth factor β2 TGFB2 1q41
Transforming growth factor β3 TGFB3 14q24
Transforming growth factor receptor beta receptor I TGFBR1 9q22
Transforming growth factor receptor beta receptor II TGFBR2 3P22
Platelet-activating factor PTAF
Platelet-activating factor receptor PTAFR 1p35-p34.3

b) The uterus and placental pathway

That includes about 10 proinflammatory factors that could, abstractly, once activated, enter the preterm birth mechanism and are encoded by specific genetic loci which, just as hypothetically, if they are altered can enter the mechanism of induction of a preterm birth or alteration of the duration of a gestation.

Coagulation Factor II F2 11p11-q12
Coagulation factor V F5 1q23
Protein C PROC 2q13-q14
β2-Adrenergic receptor Beta2-AR 5q31-q32
Vascular endothelial growth factor VEGF 6p12
Angiotensinogen AGT 1q42-q43
Apolipoprotein E APOE 19q13.2
Methylenetetrahydrofolate reductase MTHFR 1p36.3
Methylenetetrahydrofolate homocysteine methyltransferase MTR 1q43

c) The endocrine pathway

That includes about 10 proinflammatory factors that could, abstractly, once activated, enter the preterm birth mechanism and are encoded by specific genetic loci which, just as hypothetically, if they are altered can enter the mechanism of induction of a preterm birth or alteration of the duration of a gestation.

Corticotropin-releasing hormone binding protein CRHBP 5q11.2-q13.3
Adrenocorticotropin ACTH 2p23.3
Corticotropin-releasing hormone CRH 8q13
Corticotropin-releasing hormone receptor 1 CRHR1 17q12-q22
Corticotropin-releasing hormone receptor 2 CRHR2 7p14.3
Estrogen receptor 1 ESR1 6q25.1
Estrogen receptor 2 ESR2 14q23.2
Brain-derived neurotrophic factor BDNF 11p13
Dopamine receptor D2 DRD2 11q23
Progesterone receptor PGR 11q22-q23

d) The contractile mechanism pathway

That includes about 10 proinflammatory factors that could, abstractly, once activated, enter the preterm birth mechanism and are encoded by specific genetic loci which, just as hypothetically, if they are altered can enter the mechanism of induction of a preterm birth or alteration of the duration of a gestation.

Prostaglandin E receptor 3 PTGER3 1p31.2
Prostaglandin E synthase PTGES 9q34.3
Prostaglandin F receptor PTGFR 1p31.1
Cyclooxygenase 1 COX-1 9q32-q33.3
Cyclooxygenase 2 (inducible) COX-2 1q25.2-q25.3
Oxytocin OXT 20p13
Oxytocin receptor OXTR 3p25
Matrix metalloproteinase 1 MMP1 11q22.3
Matrix metalloproteinase 2 MMP2 16q13-q21
Matrix metalloproteinase 3 MMP3 11q22.3
Matrix metalloproteinase 8 MMP8 11q22.3
Matrix metalloproteinase 9 MMP9 20q11.2-q13.1
Relaxin 1 RLN1 9p24.1
Relaxin 2 RLN2 9p24.1
Relaxin 3 RLN3 19p13.2

e) The metabolic pathway

That includes about 15 proinflammatory factors that could, abstractly, once activated, enter the preterm birth mechanism and are encoded by specific genetic loci which, just as hypothetically, if they are altered can enter the mechanism of induction of a preterm birth or alteration of the duration of a gestation

Opioid receptor, mu 1 OPRM1 6q24-q25
N-Acetyltransferase 1 NAT1 8p23.1-p21.3
N-Acetyltransferase 2 NAT2 8p22
Cytochrome P450, family 1, subfamily A, polypeptide 1 CYP1A1 15q22-q24
Cytochrome P450, family 2, subfamily A, polypeptide 6 CYP2A6 19q13.2
Cytochrome P450, family 2, subfamily D, polypeptide 6 CYP2D6 22q13.1
Cytochrome P450, family 2, subfamily E, polypeptide 1 CYP2E1 10q24.3-qter
Heat shock protein 70 Hsp-70 6p21.3
Alcohol dehydrogenase 1A ADH1A 4q21-q23
Alcohol dehydrogenase 1B ADH1B 4q21-q23
Alcohol dehydrogenase 1C ADH1C 4q21-q23
Aldehyde dehydrogenase ALDH2 12q24.2