Role of 14-bp deletion/insertion polymorphism in exon 8 of the HLA-G gene in recurrent spontaneous abortion patients

Abstract

BACKGROUND:Human leukocyte antigen (HLA)-G belongs to the nonclassical Class I major histocompatibility complex, and is predominantly and specifically found on the extravillous cytotrophoblast cells of the placenta. HLA-G has been postulated as an important immunotolerant molecule in maintaining successful pregnancy and maternal tolerance of the semiallogenic fetus. Recent reports indicate that the 14-bp deletion/insertion polymorphism in exon 8 of the 3’UTR region of the HLA-G gene influences the HLA-G mRNA stability and isoform splicing patterns, thus modulating the levels of HLA-G expression.AIM:The aim was to study the 14-bp deletion/insertion polymorphism in exon 8 of the 3’UTR region of the HLA-G gene.MATERIALS AND METHODS:A total of 50 women with unexplained three or more recurrent spontaneous abortions (RSAs) and 41 normal healthy control women who have had normal pregnancies and were genotyped for the 14-bp deletion/insertion polymorphism were genotyped for the 14-bp deletion/insertion polymorphism by polymerase chain reaction for exon 8-specific primersRESULTS:It was found that the 14-bp allele deletion frequency was lower in patients (67%) versus controls (73%), while 14-bp allele insertion was higher among patients (33%) versus controls (9%). Similarly, the homozygous deletion halotype was higher among the controls (80.48%); the heterozygous insertion deletion haplotype (34%) and homozygous insertion haplotype (16%) were higher in RSA patients. The HLA haplotype HLA A*02:11_B*40:06:01:01 was increased among RSA women compared to controls.CONCLUSION:Our results suggest that 14-bp deletion/insertion polymorphisms might have importance in the outcome of pregnancy and the 14-bp deletion polymorphism in exon 8 of the HLA-G gene may be important from an evolutionary perspective of successful pregnancy.

Genetic association between the HLA-G 14-bp insertion/deletion polymorphism and the recurrent spontaneous abortions in Saudi Arabian women

“…Our results regarding the association study between the 14-bp indel polymorphism and RSA in the Saudi population agree with those reported in other populations such as the Amerindian populations from the Brazilian Amazon, Finnish, Hungarian, Polish, Japanese, Danish, Chinese, and some Indian populations (Hviid et al, 2002;Yan et al, 2006;Xue et al, 2007;Aruna et al, 2010). However, in other studies, the association between the HLA-G 14-bp polymorphism and RSA were confirmed in some Indian and Chinese populations (Shankarkumar et al, 2011). However in a previous study in an Indian population, the HLA-G 14-bp polymorphism was not associated with RSA disorder (Tripathi et al, 2004).…”

Relationship between HLA-G polymorphism and susceptibility to recurrent miscarriage: A meta-analysis of non-family-based studies

“…Among these, 4 studies were excluded due to duplicate publications [32][33][34][35], three had incomplete data on allele and genotype frequency which we failed to get by emails to the corresponding authors [36][37][38], and an additional one was excluded due to the absence of a control group [39]. Consequently, the remaining 17 case-control studies which examined the association between the HLA-G 14-bp polymorphism and RM were finally included [12,17,[25][26][27][40][41][42][43][44][45][46][47][48][49][50][51] (Fig. 1).…”

“…Association between RM and HLA-G 14-bp insertion/deletion polymorphism allele Sixteen studies were included in assessing the association between HLA-G 14-bp insertion/deletion polymorphism allele and RM [12,17,[25][26][27][40][41][42][43][44][45][46][47][48][49][50]. As shown in Fig.…”

Role of HLA-G and other immune mechanisms in pregnancy

“…Xue et al [100] reported that recurrent spontaneous abortion patients in Chinese populations have significantly more -14 bp/+14 bp heterozygotes in the 3'UT HLA-G gene region. In India, the alleles with the 14 bp insertion were also more frequent in patients with RPL compared to controls [101]. Vargas et al [102] found significantly elevated frequencies of recurrent miscarriages (RM) in Brasilian women with haplotype HLA-G*01:01:08/+14bp and HLA-G*01:04:01/-14bp.…”

“…Zhu et al, [98] recurrent spontaneous abortion PCR increasedfrequencyofthe+14bp/+14bpgenotypein RSA women compared to normal fertile controls in an Indian population Shankarkumar et al, [101] recurrent spontaneous abortion PCR significantelevatedfrequenciesofhaplotypesHLA-G*01:01:08/+14bpandHLA-G*01:04:01/-14bpinBrasilianRSA women…”