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Chlamydia trachomatis is the most common sexually transmitted bacterium worldwide. Its often asymptomatic course of infection increases chances of transmission, and increases risk of late complications. Genetic variations in the host immune system are known to impact the course of infections. Recent studies have shown a positive impact of vitamin D on the regulation of the immune system. This study assesses the impact of eight polymorphisms in five genes [VDR (rs1544410 G > A, rs2228570 C > T), CYP27B1 (rs10877012 G > T), DHCR7 (rs7944926 G > A, rs3829251 G > A), GC (rs3755967) and CYP2R1 (rs10741657 G > A, rs2060793 G > A)] on susceptibility to Chlamydia infections in humans. These polymorphisms could influence protein expression or function, and thus influence the immune system. Samples of women visiting the STD outpatient clinic in South Limburg were genotyped using the Roche Lightcycler 480. In this study, we did not observe statistically significant differences between the genotype distributions of these polymorphisms in women with or without a Chlamydia infection. This suggests that VDR, CYP27B1, DHCR7, GC and CYP2R1 do not affect the susceptibility to Chlamydia infections. However, due to its pleiotropic nature in the immune system a role for the vitamin D pathway may not be excluded from the whole clinical course of Chlamydia infections (e.g. late complications), and further research is required., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The interindividual differences in response to Chlamydia trachomatis (CT) infections are for an important part based on the differences in our host genetic make-up. In the past, several genes and pathways have been identified and linked to protection against or risk for CT infection (i.e. susceptibility), and/or the severity of infection, with a major emphasis on the development of tubal pathology, one of the main causes of female infertility. In the current study, we analyzed in Dutch Caucasian women whether the carriage of HLA-A G>A SNP (rs1655900) was related to the susceptibility of CT infection in a STD cohort (n = 329) and to the severity of infection in a subfertility cohort (n = 482). We also investigated if this A-allele was linked to increase in severity of symptoms, from mild symptoms (lower genital infection) to lower abdominal pain (upper genital tract infection) to the most severe late complication of tubal pathology, including double-sided tubal pathology. We showed that the carriage of HLA-A SNP rs1655900 studied is not associated with the susceptibility to CT infection based on the data from the STD cohort, but might be protective to the development of late complications (p = 0.0349), especially tubal pathology could be relevant., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Intracellular pattern-recognition receptors NOD1 and NOD2 are capable of sensing common structural units of bacterial walls. Recognition triggers specific immune signalling pathways and leads to pro-inflammatory cytokine upregulation and adequate immune response. We investigated whether two functional polymorphisms in NOD1 and NOD2 exert an effect on susceptibility to (STD patients) and severity of (female patients visiting the fertility clinic) Chlamydia trachomatis infection in 807 Dutch Caucasian women. A significant association of the NOD1 +32656 GG insertion variant with protection against infection with C. trachomatis has been detected [p: 0.0057; OR: 0.52]. When comparing C. trachomatis-positive women without symptoms to C. trachomatis-positive women with symptoms, and to C. trachomatis-positive women with TFI, we observed an increasing trend in carriage of the GG allele [Ptrend: 0.0003]. NOD2 1007fs failed to reveal an association. We hypothesize that the underlying mechanism might be a functional effect of the GG insertion on IFN-beta-dependent regulation of immune response in the genital tract. The research is part of an ongoing effort of identifying key polymorphisms that determine the risk of TFI and effectively translating them into the clinical setting for the purpose of optimizing diagnostic management of women at risk for developing TFI., (© The Author 2015. Published by Oxford University Press on behalf of FEMS. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)