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. 2021 Jan 7;10(1):48.
doi: 10.3390/pathogens10010048.

Can Previous Associations of Single Nucleotide Polymorphisms in the TLR2, NOD1, CXCR5, and IL10 Genes in the Susceptibility to and Severity of Chlamydia trachomatis Infections Be Confirmed?

Jelmer B Jukema  1 , Bernice M Hoenderboom  1   2 , Birgit H B van Benthem  2 , Marianne A B van der Sande  2   3   4 , Henry J C de Vries  5   6 , Christian J P A Hoebe  7   8 , Nicole H T M Dukers-Muijrers  7   8 , Caroline J Bax  9 , Servaas A Morré  1   10 , Sander Ouburg  1
Affiliations

Can Previous Associations of Single Nucleotide Polymorphisms in the TLR2, NOD1, CXCR5, and IL10 Genes in the Susceptibility to and Severity of Chlamydia trachomatis Infections Be Confirmed?

Jelmer B Jukema et al. Pathogens. .

Abstract

Clear inter-individual differences exist in the response to C. trachomatis (CT) infections and reproductive tract complications in women. Host genetic variation like single nucleotide polymorphisms (SNPs) have been associated with differences in response to CT infection, and SNPs might be used as a genetic component in a tubal-pathology predicting algorithm. Our aim was to confirm the role of four genes by investigating proven associated SNPs in the susceptibility and severity of a CT infection. A total of 1201 women from five cohorts were genotyped and analyzed for TLR2 + 2477 G > A, NOD1 + 32656 T -> GG, CXCR5 + 10950 T > C, and IL10 - 1082 A > G. Results confirmed that NOD1 + 32656 T ->GG was associated with an increased risk of a symptomatic CT infection (OR: 1.9, 95%CI: 1.1-3.4, p = 0.02), but we did not observe an association with late complications. IL10 - 1082 A > G appeared to increase the risk of late complications (i.e., ectopic pregnancy/tubal factor infertility) following a CT infection (OR = 2.8, 95%CI: 1.1-7.1, p = 0.02). Other associations were not found. Confirmatory studies are important, and large cohorts are warranted to further investigate SNPs' role in the susceptibility and severity of a CT infection.

Keywords: Chlamydia trachomatis; SNP; severity; single nucleotide polymorphism; susceptibility.

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Conflict of interest statement

S.A. Morré is besides Head of the Laboratory of Immunogenetics and founder of TubaScan Ltd. but has a 100% University-based employment. The other authors declare that they have no competing interests.

Figures

Figure A1
Figure A1
Sensitivity trend analysis using cohort (2) and a selection of cohort (1) comparing genotype distributions between women based on increased severity: (1) Fertile CT positive women. (2) CT positive women with PID. 3. CT positive women with ectopic pregnancy and/or tubal factor infertility. Percentage of genotypes as part of the total. Abbreviations: CT+, Chlamydia trachomatis positive; PID, pelvic inflammatory disease; EP, ectopic pregnancy; TFI, tubal factor infertility.
Figure 1
Figure 1
Trend analysis of Cohorts (4) and (5) Comparing genotype distributions between women based on increased severity: (1) Fertile CT positive women. (2) CT positive women with PID. (3) CT positive women with ectopic pregnancy and/or tubal factor infertility. Percentage of genotypes as part of total. Abbreviations: CT+, Chlamydia trachomatis positive; PID, pelvic inflammatory disease; EP, ectopic pregnancy; TFI, tubal factor infertility.
Figure 1
Figure 1
Trend analysis of Cohorts (4) and (5) Comparing genotype distributions between women based on increased severity: (1) Fertile CT positive women. (2) CT positive women with PID. (3) CT positive women with ectopic pregnancy and/or tubal factor infertility. Percentage of genotypes as part of total. Abbreviations: CT+, Chlamydia trachomatis positive; PID, pelvic inflammatory disease; EP, ectopic pregnancy; TFI, tubal factor infertility.
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