TY - JOUR
T1 - Examining extended human leukocyte antigen-G and HLA-F haplotypes
T2 - the HLA-G UTR-4 haplotype is associated with shorter time to pregnancy in an infertility treatment setting when both female and male partners are carriers
AU - Nilsson, Line Lynge
AU - Scheike, Thomas
AU - Langkilde, Cæcilie H.
AU - Jørgensen, Nanna
AU - Hornstrup, Micha B.
AU - Perin, Trine L.
AU - Funck, Tina
AU - Lindhard, Anette
AU - Hviid, Thomas Vauvert F.
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - assisted reproduction technologies
KW - gene variation
KW - HLA-F
KW - HLA-G
KW - Infertility
U2 - 10.1016/j.fertnstert.2020.04.052
DO - 10.1016/j.fertnstert.2020.04.052
M3 - Journal article
C2 - 32912613
AN - SCOPUS:85090318710
VL - 114
SP - 628
EP - 639
JO - Sexuality, Reproduction and Menopause
JF - Sexuality, Reproduction and Menopause
SN - 1546-2501
IS - 3
ER -