HLA-G regulatory haplotypes and implantation outcome in couples who underwent assisted reproduction treatment

Maternal human leukocyte antigen-G (HLA-G) genetic variants associate with in utero mother-to-child transmission of HIV-1 in Black South Africans

“…For example, in a study of recurrent pregnancy loss, the tri-allelic polymorphism −725C/G/T (rs1233334) within the 5’URR was evaluated in relation to plasma sHLAG concentration, and the CC genotype was found to have significantly lower levels of sHLAG than the CG and CT genotypes (Jassem et al, 2012). Additionally, it was suggested that the presence of Guanine in position −725 may alter the methylation profile of CpG dinucleotides resulting in a modification of gene expression, influencing the binding of regulatory factors as IRF-1 (Interferon response factor-1) to ISRE (interferon specific regulation element) (Costa et al, 2012). Indeed, G*01:01:02 alleles were reported in 5’URR haplotypes having the −725C allele (Costa et al, 2012).…”

Balancing immunity and tolerance: genetic footprint of natural selection in the transcriptional regulatory region of HLA-G

“…Another sequencing survey of HLA-G 5′URR concerned a 1151-bp fragment spanning nucleotides from − 1399 to − 1049 and from − 764 to +35 in 100 individuals from Southeastern Brazil (Ribeirão Preto, State of São Paulo). 12 Other previously published data were not included in the present analysis because of (a) a lack of information on the ethnicity of sampled individuals, 69 (b) a selection bias when defining the individuals to be sequenced for the HLA-G promoter region, 18 (c) a lack of frequency data provided in the published paper 19,20 and (d) a lack of allele frequency data for SNVs with MAFo0.02. 4,28 LD, tagging and haplotype analyses Strength of LD between pairs of markers was measured as D' 70 using the Haploview software v4.2, 71 and statistical significance of LD was assessed by a Fisher's exact test of LD using the Arlequin v.3.5.1.2 software.…”

“…The − 486 A4C SNV (rs114626623) was associated with increased risk of miscarriage 4 and end-stage renal disease. 28 Finally, Costa et al 19 found a significant association between HLA-G 5′URR haplotypes (including notably the putatively functional − 1140 A4T SNV (rs115371574)) and implantation outcome in couples undergoing assisted reproduction treatment. Considering the unique features of the HLA-G 5′URR among HLA class I genes, 29 and the fact that nucleotide changes in the cis-acting regulatory elements of this region may determine its differential responsiveness to transcriptional factors, 30,31 further genetic investigations are needed to clarify the role of HLA-G 5′URR polymorphisms in the spatio-temporal expression profile of HLA-G.…”

“…7,8 In contrast, the HLA-G 5′URR has been poorly studied. Only a few reports have surveyed sequence variation in this gene region in healthy individuals, 4,9,12,[18][19][20][21] providing limited knowledge of the worldwide genetic diversity at this regulatory gene segment. Similarly, there have been few attempts to associate HLA-G 5′URR variations with modulation of HLA-G expression and susceptibility to diseases.…”

“…Similarly, there have been few attempts to associate HLA-G 5′URR variations with modulation of HLA-G expression and susceptibility to diseases. 4,18,19,[22][23][24][25][26][27][28] Ober et al 18 focused on the triallelic singlenucleotide variant (SNV) − 725 C4G/T (rs115535764) and reported 1 that the fetal loss rates were highest among couples who carried the − 725 G allele, which was further associated with increased HLA-G transcription. 24 Nicolae et al 22 reported a significant association between bronchial asthma and the − 964 G4A SNV (rs115338359).…”