Preterm Birth Causes, Consequences, and Prevention (2007) / Chapter Skim
Currently Skimming:
7 Role of Gene-Environment Interactions in Preterm Birth
7 Role of Gene-Environment Interactions in Preterm Birth
Pages 207-228
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 207... ...
7 Role of Gene-Environment Interactions in Preterm Birth ABSTRACT Until recently, the role of genetic susceptibility and gene-envi ronment interactions in preterm birth has largely been unexplored. Growing evidence indicates that familial or intergenerational fac tors influence preterm birth.
|
From page 208... ...
. The improved methods for measuring nongenetic factors and environmental exposures promise to extend the scope of epidemiological investigation (Weaver et al., 1998)
|
From page 209... ...
. A population-based cohort study of data from birth certificates and fetal death certificates from the state of Georgia between 1980 and 1995 suggest that the recurrence of preterm delivery contributes to a notable portion of all preterm births, especially for the shortest gestations (Adams et al., 2000)
|
From page 210... ...
210 PRETERM BIRTH plex human diseases, such as obesity, hypertension, diabetes, and asthma, preterm birth is a complex trait and possesses the following features: nonMendelian transmission, the involvement of multiple genes, and gene-gene and gene-environment interactions. Research on the genetics of preterm birth thus faces significant challenges.
|
From page 211... ...
Studies Involving One or a Few Candidate Genes To date, most published studies on the genetics of preterm birth have examined only one or a few genes in a given study sample. The frequent association of spontaneous preterm labor and preterm birth with histological infection-inflammation and elevated concentrations of inflammatory cytokines in body fluids has focused investigations on single gene polymorphisms in the genes for these cytokines in both the mother and the fetus (Varner and Esplin, 2005)
|
From page 212... ...
A and LTA(IVS1-82) C, constituents of the AGG and GAC haplotypes, respectively, were also strongly associated with an increased risk of spontaneous preterm birth.
|
From page 213... ...
213 ROLE OF GENE-ENVIRONMENT INTERACTIONS TABLE 7-1 Potential Candidate Genes for Preterm Births Gene No. and Chromosome Pathway Gene Name Gene Location Inflammatory pathway 1 Colony-stimulating factor 1 CSF1 1p21-p13 2 Colony-stimulating factor 1 receptor CSF1R 5q33-q35 3 Colony-stimulating factor 2 CSF2 5q31.1 4 Colony-stimulating factor 2 receptor alpha CSF2RA Xp22.32 and Yp11.3 5 Colony-stimulating factor 2 receptor beta CSF2RB 22q13.1 6 Colony-stimulating factor 3 CSF3 17q11.2-q12 7 Colony-stimulating factor 3 receptor CSF3R 1p35-p34.3 8 Interferon gamma receptor 1 IFNGR1 6q23-q24 9 Interleukin-1α IL1A 2q14 10 Interleukin-1 receptor type I IL1R1 2q12 11 Interleukin-1 receptor type II IL1R2 2q12-q22 12 Interleukin-1 receptor antagonist IL1RN 2q14.2 13 Interleukin-1β IL1b 2q14 14 Interleukin-2 IL2 4q26-q27 15 Interleukin-2 receptor alpha IL2RA 10p15-p14 16 Interleukin-2 receptor beta IL2RB 22q13.1 17 Interleukin-4 IL4 5q31.1 18 Interleukin-4 receptor IL4R 16p11.2-12.1 19 Interleukin-5 IL5 5q31.1 20 Inteleukin-6 IL6 7p21 21 Interleukin-6 receptor IL6R 1q21 22 Interleukin-8 IL8 4q13-q21 23 Interleukin-8 receptor alpha IL8RA 2q35 24 Interleukin-10 IL10 1q31-q32 25 Interleukin-10 receptor alpha IL10RA 11q23 26 Interleukin-10 receptor beta IL10RB 21q22.11 27 Interleukin-11 IL11 19q13.3-q13.4 28 Interleukin-12A IL12A 3p12-q13.2 29 Interleukin-13 IL13 5q31 30 Interleukin-15 IL15 4q31 31 Interleukin-17 IL17 6p12 32 Interleukin-18 IL18 11q22.2-q22.3 33 Lymphotoxin alpha LTA 6p21.3 34 Lymphotoxin beta LTB 6p21.3 35 Nitric oxide synthase 2A NOS2A 17q11.2-q12 36 Nitric oxide synthase 3 NOS3 7q36 37 Tumor necrosis factor alpha TNFA 6p21.3 38 Type 1 tumor necrosis factor alpha receptor TNFR1 12p13.2 39 Type 2 tumor necrosis factor alpha receptor TNFR2 1p36.3-p36.2 40 Tumor necrosis factor receptor TNFRSF6 10q24.1 superfamily member 6 continued
|
From page 214... ...
214 PRETERM BIRTH TABLE 7-1 Continued Gene No. and Chromosome Pathway Gene Name Gene Location 41 Type 1 tumor necrosis factor receptor ARTS-1 5q15 shedding aminopeptidase regulator 42 Gamma interferon IFN-?
|
From page 215... ...
215 ROLE OF GENE-ENVIRONMENT INTERACTIONS TABLE 7-1 Continued Gene No. and Chromosome Pathway Gene Name Gene Location β2-Adrenergic receptor 4 Beta2-AR 5q31-q32 5 Vascular endothelial growth factor VEGF 6p12 8 Angiotensinogen AGT 1q42-q43 9 Apolipoprotein E APOE 19q13.2 10 Methylenetetrahydrofolate reductase MTHFR 1p36.3 11 Methylenetetrahydrofolate homocysteine MTR 1q43 methyltransferase Endocrine pathway 1 Corticotropin-releasing hormone binding protein CRHBP 5q11.2-q13.3 2 Adrenocorticotropin ACTH 2p23.3 3 Corticotropin-releasing hormone CRH 8q13 4 Corticotropin-releasing hormone receptor 1 CRHR1 17q12-q22 5 Corticotropin-releasing hormone receptor 2 CRHR2 7p14.3 6 Estrogen receptor 1 ESR1 6q25.1 7 Estrogen receptor 2 ESR2 14q23.2 8 Brain-derived neurotrophic factor BDNF 11p13 9 Dopamine receptor D2 DRD2 11q23 10 Progesterone receptor PGR 11q22-q23 Uterine contraction 1 Prostaglandin E receptor 2 PTGER2 14q22 2 Prostaglandin E receptor 3 PTGER3 1p31.2 3 Prostaglandin E synthase PTGES 9q34.3 4 Prostaglandin F receptor PTGFR 1p31.1 5 Cyclooxygenase 1 COX-1 9q32-q33.3 6 Cyclooxygenase 2 (inducible)
|
From page 216... ...
The data presented in the previous chapters and in this chapter suggested that both socioenvironmental factors and genetic factors may influence preterm birth. Given individual genetic variations and differential environmental exposures, stratification of study subjects by genotype may allow the detection of risk of preterm birth among individuals exposed to a
|
From page 217... ...
were found to be at a significantly increased risk of spontaneous preterm birth (OR 2.7; 95% CI 1.7–4.5)
|
From page 218... ...
218 PRETERM BIRTH EPIGENETICS DNA is not freely floating within the cell cytoplasm or nucleus; it is organized with proteins called histones to form a complex substance known as chromatin (see Box 7-1 for definition of terms)
|
From page 219... ...
While there are no data regarding the possibility of epigenetic influences on spontaneous preterm parturition, it is important to recognize the possible influence that epigenotype may have gene expression and, thus, on the functional consequences that it may have on the length of gestation. PROTEOMICS Despite the many advantages and advances in knowledge attributable to genomics and microarray analysis, these approaches have several limitations.
|
From page 220... ...
Two recent reports suggest that the detection of these peptides by proteomic analysis yields a sensitivity and a specificity in excess of 90 percent each for the detection of subclinical intra-amniotic fluid infection associated with preterm labor (Buhimschi et al., 2005; Gravett et al., 2004)
|
From page 221... ...
. An improved understanding of the early events in preeclampsia and the ability to provide an early diagnosis of this and other pregnancy-related conditions are necessary to develop rational and efficacious intervention strategies that may reduce the risks of preterm birth.
|
From page 222... ...
Allele Frequency One possible reason for a genetic influence on racial disparities in preterm birth is that susceptibility variants may be present in one population but absent in others or may vary in frequencies across diverse populations. This may affect the number of individuals at increased risk for preterm birth.
|
From page 223... ...
. METHODOLOGICAL ISSUES Although multiple genetic markers have been identified to be potentially associated with preterm birth, preterm labor, or PPROM, none of the markers has been adequately validated as a cause of preterm birth in studies with various populations and no single marker appears to be highly sensitive or specific to preterm birth, preterm labor, or PPROM.
|
From page 224... ...
, preterm labor, and preterm rupture of membranes, constitute heterogeneous groups. As such, standard genetic or epidemiological analysis may lack the power to detect the causative genes and the environmental risk factors because of the dilution effect.
|
From page 225... ...
What remains unclear are the effects of haplotyping error because of the uncertainty of the inference drawn from the results of the derivation of the SNP block structure and subsequent association tests obtained with unrelated diploid subjects. Population Admixture A source of potential confounding in genetic tests is a hidden population genetic structure.
|
From page 226... ...
Understanding of these effects may also allow recurrence risk counseling. However, given the correlation between maternal and offspring genotypes, the relative importance of these two interrelated risk factors (or of their interactions with exposures)
|
From page 227... ...
227 ROLE OF GENE-ENVIRONMENT INTERACTIONS Sample Size and Power In studies of gene-environment interactions, it is difficult to obtain the correct sample size and power estimate, and there are no well-established methods for doing so. Efforts to study complex gene-environment interactions are also tempered by the difficulty of obtaining adequate sample sizes.
|
From page 228... ...
CONCLUSION For many years, research on the etiology of preterm birth has primarily focused on demographic, social-behavioral, and environmental risk factors. Until recently, the roles of genetic susceptibility and gene-environment interactions in preterm birth have largely been unexplored.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.