Intronic variants of LGALS13 gene encoding placental protein (PP13) are linked with increased risk of infection-associated spontaneous preterm birth

Abstract

Problem: Spontaneous preterm birth (sPTB) is a global health issue. Studies suggest infection and infection-based inflammatory responses are major risk factors for sPTB. Considering the important role of anti-inflammatory proteins in pregnancy, the study aimed to find the association between anti-inflammatory LGALS13 gene variants IVS2-22 A/G (rs2233706) and IVS3+72 T/A (rs2233708) and the risk of sPTB during Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum infection in Indian population.

Method of study: Placental samples of 160 sPTB and 160 term women were collected. Pathogens were detected by PCR. The genotyping of LGALS13 gene variants IVS2-22 A/G (rs2233706) and IVS3+72 T/A (rs2233708) was done by qualitative real-time PCR using allelic discrimination method (VIC- and FAM-labeled).

Results: The frequency of AG or GG genotype of LGALS13 IVS2-22A/G polymorphism (rs2233706) was 75.5% in infected sPTB cases and 14.4% in uninfected sPTB cases and 7.3% in term birth controls (p < .0001), while the frequency of TA or AA genotype of LGALS13 IVS3+72T/A polymorphism (rs2233708) was 83.6% in infected sPTB cases and 18% in uninfected sPTB cases and 12.7% in term birth controls (p < .0001). The genotypic frequencies for both the variants of LGALS13 were statistically significant (p < .0001) in the infected sPTB versus uninfected sPTB and term birth controls.

Conclusions: Study reveals strong association between the presence of immunological gene variants LGALS13 IVS2-22 A/G (rs2233706) and LGALS13 IVS3+72 T/A (rs2233708) and risk of sPTB during C. trachomatis, M. hominis and U. urealyticum infection.

Keywords: Chlamydia trachomatis; LGALS13; Mycoplasma hominis; Ureaplasma urealyticum; preterm birth.