Linkage Disequilibrium Between Human Leukocyte Antigen (HLA) Class II and HLA-G—Possible Implications for Human Reproduction and Autoimmune Disease

Hviid, Thomas Vauvert F.; Christiansen, Ole Bjarne

doi:10.1016/j.humimm.2005.03.003

Cited by 80 publications

(65 citation statements)

References 86 publications

(97 reference statements)

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“…Neither the individual carriage of HLA-DRB1 * 01 and -DRB1 * 03 nor the carriage of HLA-G * 010102 alone increased the risk of RM compared with the carriage of none of the alleles. However, carriage of HLA-DRB1 * 01 or -DRB1 * 03 together with the HLA-G * 010102 allele was associated with an OR = 4 for RM [65] . This may reflect epistatic interaction of polymorphisms located in the same genetic region.…”

Section: Genetics Of Rmmentioning

confidence: 87%

Multifactorial Etiology of Recurrent Miscarriage and Its Scientific and Clinical Implications

Christiansen

Steffensen

Nielsen

et al. 2008

Gynecol Obstet Invest

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156

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A considerable proportion of recurrent miscarriage (RM) cases are caused by recurrent chromosomally abnormal conceptions. However, in younger patients and patients with multiple miscarriages, maternal causes seem to dominate. No single biomarker with a high predictive value of maternally caused RM has been identified. Non-genetic biomarkers in RM may not reflect conditions in the pregnant uterus and we rarely know whether they are causes or consequences of miscarriage. Studies of genetic biomarkers are probably the best way to reveal the pathophysiological mechanisms behind RM. Epidemiological and genetic studies suggest that RM due to maternal causes has a multifactorial background. The risk of RM in each patient is probably determined by the interaction of many genetic variants and environmental factors but only few of these have so far been identified. The genetic biomarkers for RM can probably be classified into three groups: (1) variants associated with excessive inflammatory responses and autoimmunity; (2) variants of importance for insulin and androgen sensitivity and turn-over, and (3) variants associated with thrombophilia. Identification of these markers will require whole genome association studies comprising thousands of individuals. Acknowledgement of the multifactorial background for RM has important implications for the management of patients in clinical practice.

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Section: Genetics Of Rmmentioning

confidence: 87%

Multifactorial Etiology of Recurrent Miscarriage and Its Scientific and Clinical Implications

Christiansen

Steffensen

Nielsen

et al. 2008

Gynecol Obstet Invest

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156

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“…Since couples who ''match'' produce offspring with HLA-DR alleles that do not differ from maternal alleles, it implies that ''matching'' of maternal and fetal HLA-DR genotypes, another particular MFG combination, is a risk factor for spontaneous abortion. Some recent studies suggest that recurrent spontaneous abortion is associated with HLA-DRB1 Ã 03 allele in the maternal genotype [Hviid and Christiansen, 2005;Kruse et al, 2004], thus an independent HLA-DRB1 Ã 03 maternal allele effect may also be a risk factor for spontaneous abortion. Hence, HLA class II or HLA-DRB1 loci might mediate the risk for spontaneous abortion as well as for systemic sclerosis and RA [Jawaheer et al, 1996;Ober et al, 1998].…”

Section: Introductionmentioning

confidence: 99%

The v‐MFG test: investigating maternal, offspring and maternal‐fetal genetic incompatibility effects on disease and viability

Hsieh

Palmer

Harney

et al. 2006

Genetic Epidemiology

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The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

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“…[93] Since HLA is a relatively small chromosome region (<3 Mbp), LD between Class I and Class II can be expected and was indeed shown, for instance, in the locus encompassing the three Class II DRB1*03-DQA1*05-DQB1*02, on the one hand and the Class I G*01010 2 in the other hand G*010102 is the HLA-G haplotype that encompasses the 14-bp sequence variant. [94] This result could put forward the idea that only one of these genes is actually modulating implantation success, according to the alleles displayed by the patient.…”

Section: "Wrong" Hla Programmingmentioning

confidence: 99%

Genetic regulation of recurrent spontaneous abortion in humans

Vaiman¹

2015

Biomed J

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Recurrent pregnancy loss, defined as a pregnancy failure occurring before 24 weeks of gestation more than two or three times according to most definitions, is a fertility defect encountered in 1-5% of the patients. This defect is of course of multifactorial origin. Among the possible origins of recurrent pregnancy loss are uterine structural defaults, defective ploidy control of the embryo, defective immunological dialog between the embryo (or the fetus) and the uterus sometimes in relation with immunological disorders (such as autoimmune diseases), thrombophilia, and free radical metabolism imbalance. Numerous studies attempted to correlate variants of genes supposed to be intervening in the different facets of the early maternal-fetal or maternal-embryonic dialog, and eventually modify the outcome of fertilization, leading to success or failure of post-implantation development. The objective of the present review is to portray the major genes and gene polymorphisms studied for their putative association with recurrent pregnancy loss. Most of these genes have been studied as candidate genes for which strong biological arguments were put forward as to their putative involvement in recurrent pregnancy loss. They were mostly studied by genetic analysis, often in various populations of different ethnic origins, throughout the world. Some of these studies were available only in English as abstracts and were nevertheless used if the information was given with enough detail. With the space being too short to depict all the available literature, different major pathways releva nt to the scientific question are presented without any attempt to hide the fact that discordant views often aroused for a given gene. rather attempt to categorize the factors that were analyzed according to their biological functions and summarize their putative effects.

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Linkage Disequilibrium Between Human Leukocyte Antigen (HLA) Class II and HLA-G—Possible Implications for Human Reproduction and Autoimmune Disease

Cited by 80 publications

References 86 publications

Multifactorial Etiology of Recurrent Miscarriage and Its Scientific and Clinical Implications

Multifactorial Etiology of Recurrent Miscarriage and Its Scientific and Clinical Implications

The v‐MFG test: investigating maternal, offspring and maternal‐fetal genetic incompatibility effects on disease and viability

Genetic regulation of recurrent spontaneous abortion in humans

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