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 |