Our data suggest that KIR2DL4 might play a crucial implication for human pregnancy.

Human leukocyte antigen (HLA)-G has been postulated as an important immunotolerant molecule in maintaining fetal-maternal relationship. Recent reports indicated that the 14-bp deletion/insertion polymorphism in exon 8 of HLA-G gene influences HLA-G mRNA stability and isoform splicing patterns, thus modulating the levels of HLA-G expression. This might play an immunomodulatory role of HLA-G during implantation and pregnancy. In the present study, 109 unrelated fertile control women and 79 women who had experienced recurrent spontaneous abortion (RSA) were genotyped for the 14-bp insertion/deletion polymorphism. No significant difference was observed in the distribution of 14-bp insertion/deletion genotype between controls and the RSA group. However, a greater number of 14-bp insertion alleles exist in the RSA group than in the controls.

Human leukocyte antigen-G (HLA-G) expression is a potential factor for the pathogenesis of virus infection. A 14 bp insertion/deletion polymorphism (rs16375) in the 3'-untranslated region of the HLA-G gene is involved in the stability of HLA-G mRNA and HLA-G protein expression. Therefore, the HLA-G 14 bp polymorphism might be involved in human cytomegalovirus (hCMV) infection. To test a possible association between the HLA-G 14 bp deletion/insertion polymorphism and the active hCMV infection, in this study, a total of 54 patients with active hCMV infection and 165 age- and sex-matched, unrelated, normal Chinese Han population were genotyped for the 14 bp insertion/deletion polymorphism. Association of 14 bp polymorphism with hCMV urine DNA copies and the odds ratio (OR) of the polymorphism as a risk factor for active hCMV infection were analyzed. Our results showed that the prevalence of -14 bp/ -14 bp genotype in active hCMV patients was markedly increased [P(c) = 0.00034, OR = 3.31, 95% confidence interval (CI): 1.77-6.18], and similar significance was also observed for the frequency of -14 bp allele (P c = 0.0023, OR = 2.24, 95% CI: 1.38-3.64) when compared with that of healthy controls. Furthermore, urine hCMV DNA copies in patients with the -14 bp/ -14 bp genotype were significantly higher than those in patients with the +14 bp/ +14 bp genotype (P = 0.041). Our findings support a potential role of HLA-G 14 bp insertion/deletion polymorphism as a susceptible factor for the active hCMV infection.

Human leukocyte antigen (HLA)-G molecule acts as a potential factor for the regulation of immune responses and its expression in virus-infected cells may enable them to escape immunosurveillance. Besides its polymorphic promoter region, the 3' untranslated region (UTR) seems to play an important role in regulating HLA-G expression. In this study, we investigated the influence of HLA-G 14 bp (rs66554220) and +3142 (rs1063320) polymorphisms in 179 women with active human papillomavirus (HPV) infection and 143 age-matched, unrelated, HPV-negative, normal Chinese Han population. Our findings showed that frequency of the allele +3142 C [31.3% vs 44.4%, odds ratio (OR) = 0.57, Pc < 0.01] and the genotype +3142 CC (10.6% vs 21.7%, OR = 0.43, Pc = 0.012) was significantly decreased in HPV infected patients compared with normal controls. Furthermore, the haplotype -14 bp/C was associated with a reduced risk for HPV infection (OR = 0.57, Pc = 0.001). Our findings also showed that HLA-G homozygous +14 bp/+14 bp genotype was significantly associated with an increased risk for HPV18 infection (OR = 12.95, P < 0.01), whereas HLA-G heterozygous +14 bp/-14 bp genotype increased risk for HPV58 (OR = 5.55, P < 0.05). Furthermore, frequency of the haplotype +14 bp/G was significantly increased in HPV18 infected patients (60.0% vs 27.3%, OR = 4.00, Pc < 0.05). Taken together, our results supported a role of the HLA-G 3' UTR polymorphisms as a susceptible factor for the active HPV infection, and suggested a possible interference of the HLA-G molecule in the response to virus infection.

BackgroundPrevious observational studies regarding the existence of an association between folate intake and the risk of breast cancer have been inconsistent. This study aimed to summarize the evidence regarding this relationship using a dose-response meta-analytic approach.Methodology and Principal FindingsWe performed electronic searches of the PubMed, EmBase, and Cochrane Library databases to identify studies published through June 2013. Only prospective observational studies that reported breast cancer effect estimates with 95% confidence intervals (CIs) for more than 2 folate intake categories were included. We excluded traditional case-control studies because of possible bias from various confounding factors. Overall, we included 14 prospective studies that reported data on 677,858 individuals. Folate intake had little effect on the breast cancer risk (relative risk (RR) for highest versus lowest category = 0.97; 95% CI, 0.90–1.05; P = 0.451). Dose-response meta-analysis also suggested that a 100 µg/day increase in folate intake had no significant effect on the risk of breast cancer (RR = 0.99; 95% CI, 0.98–1.01; P = 0.361). Furthermore, we used restricted cubic splines to evaluate the nonlinear relationship between folate intake and the risk of breast cancer, and discovered a potential J-shaped correlation between folate intake and breast cancer risk (P = 0.007) and revealed that a daily folate intake of 200–320 µg was associated with a lower breast cancer risk; however, the breast cancer risk increased significantly with a daily folate intake >400 µg.Conclusion/SignificanceOur study revealed that folate intake had little or no effect on the risk of breast cancer; moreover, a dose-response meta-analysis suggested a J-shaped association between folate intake and breast cancer.