Correction: Intrahepatic Cholestasis of Pregnancy (ICP) in U.S. Latinas and Chileans: Clinical features, Ancestry Analysis, and Admixture Mapping.
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ABSTRACT:
SUBMITTER: PLOS ONE Staff
PROVIDER: S-EPMC4552637 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Correction: Intrahepatic Cholestasis of Pregnancy (ICP) in U.S. Latinas and Chileans: Clinical features, Ancestry Analysis, and Admixture Mapping.
PloS one 20150828 8
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Project description:In the Americas, women with Indigenous American ancestry are at increased risk of intrahepatic cholestasis of pregnancy (ICP), relative to women of other ethnicities. We hypothesized that ancestry-related genetic factors contribute to this increased risk. We collected clinical and laboratory data, and performed biochemical assays on samples from U.S. Latinas and Chilean women, with and without ICP. The study sample included 198 women with ICP (90 from California, U.S., and 108 from Chile) and 174 pregnant control women (69 from California, U.S., and 105 from Chile). SNP genotyping was performed using Affymetrix arrays. We compared overall genetic ancestry between cases and controls, and used a genome-wide admixture mapping approach to screen for ICP susceptibility loci. We identified commonalities and differences in features of ICP between the 2 countries and determined that cases had a greater proportion of Indigenous American ancestry than did controls (p = 0.034). We performed admixture mapping, taking country of origin into account, and identified one locus for which Native American ancestry was associated with increased risk of ICP at a genome-wide level of significance (P = 3.1 x 10(-5), Pcorrected = 0.035). This locus has an odds ratio of 4.48 (95% CI: 2.21-9.06) for 2 versus zero Indigenous American chromosomes. This locus lies on chromosome 2, with a 10 Mb 95% confidence interval which does not contain any previously identified hereditary 'cholestasis genes.' Our results indicate that genetic factors contribute to the risk of developing ICP in the Americas, and support the utility of clinical and genetic studies of ethnically mixed populations for increasing our understanding of ICP.
| S-EPMC4488338 | biostudies-literature
Project description:DNA microarray was applied to characterize the whole-genome expression profiles of placentas during ICP development.
2013-04-18 | GSE46157 | GEO
Project description:DNA microarray was applied to characterize the whole-genome expression profiles of placentas during ICP development. Pregnant women were categorized evenly into three groups: healthy group; mild ICP, with serum bile-acid concentration ranging from 10M-bM-^@M-^S40 uM; and severe ICP, with bile-acid concentration >40 uM.
2013-04-18 | E-GEOD-46157 | biostudies-arrayexpress
Project description:Evaluation of Ancestry Admixture among Chileans
| PRJNA391040 | ENA
Project description: Not available
| S-EPMC9828981 | biostudies-literature
Project description:U.S. Latinas have a lower incidence of breast cancer compared with non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their genetic ancestry from Europeans and Indigenous Americans. We used genetic markers to estimate the ancestry of Latina breast cancer cases and controls and assessed the association with genetic ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 ancestry informative markers in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco Bay area and estimated genetic ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (95% CI) for ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European ancestry was associated with increased breast cancer risk. The OR for a 25% increase in European ancestry was 1.79 (95% CI, 1.28-2.79; P<0.001). When known risk factors and place of birth were adjusted for, the association with European ancestry was attenuated but remained statistically significant (OR, 1.39; 95% CI, 1.06-2.11; P=0.013). Further work is needed to determine if the association is due to genetic differences between populations or possibly due to environmental factors not measured.
| S-EPMC2674787 | biostudies-literature
Project description:LncRNA plays a crucial role in human disease. However, the expression and function of LncRNA in ICP(Intrahepatic cholestasis of pregnancy) is still not fully elucidated. In this study, we found Linc02527 was increased expression in placenta and serum of ICP patients. Ectopically expression of Linc02527 promoted autophagy and proliferate in HTR8 cells. Silencing Linc02527 suppressed the autophagy and proliferate in HTR8 cells. Mechanically study revealed that Linc02527 regulated the expression of ATG5 and ATG7 by sponging miR-3185. Linc02527 directly binding to YBX1 and activated P21. The growth of C57 mouse was retarded when autophagy was activated. In normal condition, inhibited autophagy using chloroquine did not affect the growth of C57 mouse. However, in the condition of autophagy was activated, inhibited autophagy using chloroquine can improve the growth of C57 mouse. Overall, the results of this study identified Linc02527 as a candidate biomarker in ICP and a potential target for ICP therapy. Chloroquine was a potential drug for ICP therapy.
| S-EPMC6155230 | biostudies-literature
Project description: Not available
| S-EPMC7389072 | biostudies-literature
Project description:Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, causes maternal pruritus and liver impairment, and may be complicated by spontaneous preterm labour, fetal asphyxial events and intrauterine death. Our understanding of the aetiology of this disease has expanded significantly in the last decade due to a better understanding of the role played by genetic factors. In particular, advances in our knowledge of bile homeostasis has led to the identification of genes that play a considerable role in susceptibility to ICP. In this review we consider these advances and discuss the disease in the context of bile synthesis and metabolism, focusing on the genetic discoveries that have shed light on the molecular aetiology and pathophysiology of the condition.
| S-EPMC4989713 | biostudies-literature
Project description:AIM:To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome. METHODS:We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique. RESULTS:Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0.05). ICP women delivered at earlier gestational age than control (p < 0.001). Foetal distress was recorded in two babies, but we failed to find any correlation between bile salt concentration and foetal distress. Twenty genes potentially correlated with ICP were found differentially expressed (p < 0.05). Among these, three belong to genetic classes involved in pathogenic mechanisms of ICP: (1) pathophysiology of pruritus (GABRA2, cases versus controls = 2, upregulated gene); (2) lipid metabolism and bile composition (HLPT, cases versus controls = 0.6, down-regulated gene) and (3) protein trafficking and cytoskeleton arrangement (KIFC3, cases versus controls = 0.5, down-regulated gene). CONCLUSIONS:Different gene expression may contribute to the complex pathogenesis of ICP. An upregulation of GABRA2 receptor may indicate that GABA may play a role in the pathogenesis of pruritus in this condition.
| S-EPMC6333085 | biostudies-literature