Showing posts with label Association. Show all posts
Showing posts with label Association. Show all posts

Tuesday, March 29, 2011

The association of maternal factors with delayed implantation and the initial rise of urinary human chorionic gonadotrophin

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A.M.Z. Jukic1,*, C.R. Weinberg2, D.D. Baird1 and A.J. Wilcox1
1Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, MD A3-05, Durham, NC 27709, USA
2Biostatistics Branch, National Institute of Environmental Health Sciences, PO Box 12233, MD A3-05, Durham, NC 27709, USA *Correspondence address. E-mail: jukica{at}niehs.nih.govReceived August 4, 2010. Revision received January 5, 2011. Accepted January 11, 2011. BACKGROUND Late implantation and the pattern of early rise in hCG have been associated with early pregnancy loss. We explored factors that might be predictive of these markers of poor embryonic health in spontaneously conceived pregnancies.

METHODS Participants in the North Carolina Early Pregnancy Study collected daily first-morning urine specimens while attempting to conceive. Samples were assayed for estrogen and progesterone metabolites (to identify day of ovulation) and hCG (to detect conception). Data were available for 190 pregnancies, 48 of which ended in early loss (within 6 weeks of the last menstrual period). We used logistic regression to identify characteristics associated with late implantation (=10 days post-ovulation). For pregnancies surviving at least 6 weeks (n= 142), we used linear mixed models to identify factors associated with variations in hCG rise in the first 7 days from detection.

RESULTS Later implantation was associated with current maternal smoking [odds ratio (OR): 5.7; 95% confidence interval (CI): 1.1–30] and with oocytes that were likely to have been fertilized late in their post-ovulatory lifespan (OR: 5.1; CI: 1.9–16). Older women had a faster rise in hCG (P= 0.01), as did women who had relatively late menarche (P for trend = 0.02). Women exposed in utero to diethylstilbestrol showed an unusual pattern of slow initial hCG rise followed by a fast increase, a pattern significantly different from that of unexposed women (P= 0.002).

CONCLUSIONS Although limited by small numbers and infrequent exposures, our analyses suggest that a woman's exposures both early in life and at the time of pregnancy may influence early development of the conceptus.

Published by Oxford University Press 2011This ArticleHum. Reprod. (2011) 26 (4): 920-926. doi: 10.1093/humrep/der009 First published online: February 2, 2011

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Sunday, March 27, 2011

Novel alleles of HLA-DQ and -DR loci show association with recurrent miscarriages among South Indian women

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Meka Aruna1, Theeya Nagaraja1, Sadaranga Andal Bhaskar2, Surapaneni Tarakeswari3, Alla Govardhan Reddy4, Kumarasamy Thangaraj4, Lalji Singh4 and B. Mohan Reddy1,*
1Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Street No. 8, Habsiguda, Hyderabad 500007, India
2Lakshmi Fertility Clinic, Pogathota, Nellore 524001, India
3Fernandez Hospital, Bogulkunta, Hyderabad 500001, India
4Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India *Correspondence address. E-mail: bmr{at}isi.ac.in; bmrisi{at}gmail.comReceived March 24, 2010. Revision received January 9, 2011. Accepted January 17, 2011. BACKGROUND In this study, recurrent miscarriages (RMs) are defined as loss of two or more clinically detectable pregnancies before 20 weeks of gestation. HLA has been thought to play a role in RM. However, the results of earlier studies on the role of different human leucocyte antigen (HLA) genes were conflicting and inconclusive. In the present study, we investigate HLA genes (HLA-DRA, HLA-DRB1, HLA-DQA1 and HLA-DQB1) in RM couples with unknown etiology and normal couples.

METHODS Blood samples from 143 RM couples and 150 control couples were analyzed, firstly to validate previously reported association studies and secondly to explore whether any novel alleles or haplotypes specific to Indian populations can be observed to be associated with RM. HLA typing was carried out by DNA sequencing.

RESULTS Results suggest an association of the DQB1*03:03:02 allele with RM (odd ratio = 2.66; pc = 0.02; confidence interval = 1.47–4.84). Haplotypes of the DQA1 and DQB1 risk alleles also showed a significant association with RM, albeit not after Bonferroni correction for multiple comparisons.

CONCLUSIONS HLA-DQB1 appears to have a strong involvement in the manifestation of RM in this population from South India. The current genetic analysis of RM and control couples not only highlights the genes exhibiting a strong etiological role but also reflects the protective nature of some HLA genes against RM. Nevertheless, most of these alleles/haplotypes were not those that are implicated in RM in other ethnic backgrounds, and hence require further validation in other populations of India, from different ethnic and/or geographic backgrounds.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 765-774. doi: 10.1093/humrep/der024 First published online: February 15, 2011

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.



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Friday, March 25, 2011

Association of polymorphisms/haplotypes of the genes encoding vascular endothelial growth factor and its KDR receptor with recurrent pregnancy loss

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Mei-Tsz Su1,2, Sheng-Hsiang Lin2, I-Wen Lee1, Yi-Chi Chen3 and Pao-Lin Kuo1,*
1Division of Genetics, Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 704, Taiwan
2Graduate Institute of Clinical Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan
3Department of Economics, National Cheng Kung University, Tainan, Taiwan *Correspondence address. Fax: +886-6-276-6185; E-mail: paolink{at}mail.ncku.edu.twReceived October 17, 2010. Revision received November 22, 2010. Accepted December 17, 2010. BACKGROUND Vascular endothelial growth factor (VEGF) and its kinase insert domain receptor (KDR) play an important role in angiogenesis, and their gene expression patterns also suggest a close relationship with early pregnancy. However, limited information is available regarding the role of the VEGF system, especially its KDR receptor, in recurrent pregnancy loss (RPL). This study was conducted to investigate a genetic association between VEGF and its receptor gene (KDR) with idiopathic RPL.

METHODS In this case–control study, 115 women who had experienced at least two consecutive spontaneous miscarriages (n= 62 women with two miscarriages, n= 53 with three or more) and 170 controls were included. A total of 14 tag single-nucleotide polymorphisms (SNPs) of VEGF and KDR were selected from the HapMap Web site and three functional SNPs [rs1570360 (-1154G/A) of VEGF; rs2305948 (V297I) and rs1870377 (Q472H) of the KDR gene] were genotyped using primer extension analysis. We further used multifactor dimensionality reduction analysis to evaluate gene–gene interactions.

RESULTS One tag SNP (rs6838752) and the functional SNP (Q472H) of the KDR gene were in complete linkage and showed significant differences between patients and controls (P< 0.05). The frequencies of haplotypes of VEGF (A-T-G haplotype) and KDR (A-C-A-T-G haplotype) showed significant differences in patients versus controls (P< 0.05). All comparisons with controls remained significant when the subgroup of women with three or more miscarriages was analyzed.

CONCLUSIONS VEGF and its receptor gene (KDR) are associated with idiopathic RPL. The VEGF/KDR system jointly contributes to recurrent miscarriage in Taiwanese Han women.

© The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com This ArticleHum. Reprod. (2011) 26 (4): 758-764. doi: 10.1093/humrep/deq401 First published online: January 20, 2011

Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.



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