title: Implication of HLA-G 5' upstream regulatory region polymorphisms in idiopathic recurrent spontaneous abortions.
abstract: The effect of HLA-G 5'-upstream regulatory region (URR) single nucleotide polymorphisms (SNP) in idiopathic recurrent spontaneous abortion (RSA) was evaluated. Parental genotype combination analysis and HLA-G expression at transcriptional level was evaluated for 5'URR SNP, which have shown increased risk for idiopathic RSA. If a fetus were aneuploid, attributing causation to a HLA-G 5'-URR SNP would be illogical; therefore couples with abnormal parental karyotypes and also those with abortus material that revealed chromosomal abnormalities were excluded. One hundred women who had experienced idiopathic RSA, along with their respective male partners and 100 pairs of control couples, were studied. HLA-G 5'-URR SNP were evaluated through sequencing. Quantitative polymerase chain reaction was used for HLA-G expression analysis. An increased risk for idiopathic RSA cases among women carriers of mutant genotypes of -1179G>A(rs1233335), -725C>G/T(rs915670) and -486A>C(rs114252012) SNP. The parental genotype combination analysis revealed a 3.5-fold increased risk for -1179G>A and 4.3-fold increased risk for -725C>G/T SNP among carriers of mutant parental genotypes in couples who have experienced idiopathic RSA. Down-regulation in HLA-G expression was seen at transcriptional level for -1179G>A and -725C>G/T SNPs in cases of idiopathic RSA. Transmission of a mutant allele from single carrier parents may, therefore, affect pregnancy outcome.
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Agrawal
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.
authors.forename: Swayam
authors.initials: S
authors.lastname: Prakash
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.
authors.forename: Maneesh Kumar
authors.initials: MK
authors.lastname: Misra
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.
authors.forename: Shubha R
authors.initials: SR
authors.lastname: Phadke
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India. Electronic address: suraksha@sgpgi.ac.in.
authors.forename: Suraksha
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D000465:Algorithms; D000483:Alleles; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059951:HLA-G Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors
chemical_list: D059951:HLA-G Antigens; D012333:RNA, Messenger
keywords: 5′ upstream regulatory region; HLA-G; idiopathic recurrent miscarriages; pregnancy outcome; single nucleotide polymorphism