Line Lynge Nilsson1, Thomas Scheike2, Cæcilie H Langkilde1, Nanna Jørgensen1, Micha B Hornstrup3, Trine L Perin3, Tina Funck4, Anette Lindhard3, Thomas Vauvert F Hviid5. 1. Center for Immune Regulation and Reproductive Immunology (CIRRI), Dept. of Clinical Biochemistry, the ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 2. Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. 3. The Fertility Clinic, Department of Obstetrics and Gynecology, the ReproHealth Research Consortium, Zealand University Hospital, Køge, Denmark. 4. Center for Immune Regulation and Reproductive Immunology (CIRRI), Dept. of Clinical Biochemistry, the ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark. 5. Center for Immune Regulation and Reproductive Immunology (CIRRI), Dept. of Clinical Biochemistry, the ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: tvh@regionsjaelland.dk.
Abstract
OBJECTIVE: To study the impact of extended human leukocyte antigen (HLA)-G and HLA-F haplotypes on time to pregnancy as measured by the number of treatment cycles in a cohort of couples in infertility treatment. DESIGN: Prospective cohort study of couples undergoing infertility treatment. SETTING: University hospital. PATIENT(S): A cohort of 127 couples and four single women in infertility treatment. INTERVENTION(S): Next-generation sequencing of the HLA-G gene and genotyping of three HLA-F locus single-nucleotide polymorphisms (SNPs). MAIN OUTCOME MEASURE(S): Extended HLA-F.HLA-G haplotypes, HLA-G promoter haplotypes and HLA-G 3'UTR haplotypes and their association with time to pregnancy as measured by number of treatment cycles until achievement of pregnancy with a live birth. Linkage disequilibrium between HLA-G variations and three HLA-F locus SNPs that impact time to pregnancy. RESULT(S): The effect of the HLA-G 3'UTR haplotype, UTR-4, was significantly increased, or modified, if the partner was a carrier compared to being a noncarrier. Extended HLA-F.HLA-G haplotypes, HLA-G promoter haplotypes, and the HLA-G 14 bp indel of the female partners were not associated with time to pregnancy. However, a trend for an association of the HLA-G 14bp insertion allele with a higher frequency of miscarriage than the 14bp deletion allele was observed. Certain HLA-G variations are in linkage disequilibrium with three HLA-F locus SNPs that influence time to pregnancy. CONCLUSION(S): HLA-G UTR-4 is significantly associated with time to pregnancy in couples undergoing infertility treatment. The findings could imply that both male and female HLA class Ib genetics have clinical relevance in reproduction.
OBJECTIVE: To study the impact of extended human leukocyte antigen (HLA)-G and HLA-F haplotypes on time to pregnancy as measured by the number of treatment cycles in a cohort of couples in infertility treatment. DESIGN: Prospective cohort study of couples undergoing infertility treatment. SETTING: University hospital. PATIENT(S): A cohort of 127 couples and four single women in infertility treatment. INTERVENTION(S): Next-generation sequencing of the HLA-G gene and genotyping of three HLA-F locus single-nucleotide polymorphisms (SNPs). MAIN OUTCOME MEASURE(S): Extended HLA-F.HLA-G haplotypes, HLA-G promoter haplotypes and HLA-G 3'UTR haplotypes and their association with time to pregnancy as measured by number of treatment cycles until achievement of pregnancy with a live birth. Linkage disequilibrium between HLA-G variations and three HLA-F locus SNPs that impact time to pregnancy. RESULT(S): The effect of the HLA-G 3'UTR haplotype, UTR-4, was significantly increased, or modified, if the partner was a carrier compared to being a noncarrier. Extended HLA-F.HLA-G haplotypes, HLA-G promoter haplotypes, and the HLA-G 14 bp indel of the female partners were not associated with time to pregnancy. However, a trend for an association of the HLA-G 14bp insertion allele with a higher frequency of miscarriage than the 14bp deletion allele was observed. Certain HLA-G variations are in linkage disequilibrium with three HLA-F locus SNPs that influence time to pregnancy. CONCLUSION(S): HLA-G UTR-4 is significantly associated with time to pregnancy in couples undergoing infertility treatment. The findings could imply that both male and female HLA class Ib genetics have clinical relevance in reproduction.
Authors: Karolina Piekarska; Paweł Radwan; Agnieszka Tarnowska; Andrzej Wiśniewski; Rafał Krasiński; Michał Radwan; Jacek R Wilczyński; Andrzej Malinowski; Izabela Nowak Journal: Front Immunol Date: 2022-01-17 Impact factor: 7.561