OBJECTIVE
The relationship of the HLA-G gene polymorphism (rs41551813, rs12722477, rs41557518 and rs66554220), perinatal infections and smoking in the family with the risk of congenital malformations (CMs) in the fetus were studied.
MATERIAL AND METHODS
We studied 335 women with offspring’s with CMs, and 418 women with one or more healthy fetuses/children. The infectious status of women was assessed based on the data of laboratory tests: microscopic examination (detection of bacterial vaginosis and vulvovaginal candidiasis, Treponema pallidum), enzyme immunoassay and polymerase chain reaction (PCR, detection of herpes simplex virus type I and II, cytomegalovirus and etc.; Neisseria gonorrhoeae, Chlamydia trachomatis and etc.). The family smoking factor was assessed as smoking by one or both partners smoking. Typing of polymorphisms of Thr31Ser (rs41551813, HLA-G*01:03) in exon 2, Leu110Ile (rs12722477, HLA-G*01:04) and 1597 delC (rs41557518, HLA-G*01:05N) in exon 3 HLA-G genes were performed by real-time PCR followed by melting analysis. HLA-G 14 bp Ins/Del polymorphism (rs66554220) was detected by PCR amplification; the amplified products were run on 7% non-denaturing polyacrylamide gel electrophoresis.
RESULTS
The study showed, maternal perinatal infections (OR=1.75 [1.31—2.34]) and smoking in the family (OR=1.75 [1.31—2.34]) were the main risk factors for CMs in fetus (P<0.001). The HLA-G 110Ile allele (rs12722477, HLA-G*01:04) in mother was detected an additional risk factor of fetal CM after adjusting for perinatal infections and smoking in the family (OR=1.86 [1.13—3.05], Pc=0.03). No association of rs41551813, rs41557518 and rs66554220 gene polymorphisms with the risk of CMs in fetus was identified.
CONCLUSION
Maternal perinatal infections, smoking in the family and rs12722477 HLA-G gene polymorphism in mother may be risk factors for CMs in the fetus. Our results can be useful in understanding the molecular mechanisms of development of pathology formation in the mother-fetus system.