Association between Cytotoxic T-Lymphocyte Antigen - 4 +49A>G Variant and Reduced Risk of Recurrent Spontaneous Abortion in Indian Bengali Population: A Case-Control Study.

Abstract

Background: Miscarriage is defined as a spontaneous loss of pregnancy before 20 weeks of gestation. According to ASRM and ESHRE, two or more consecutive pregnancy losses are referred to as recurrent spontaneous abortion (RSA). Approximately 15% women are at risk of miscarriage worldwide and 7.4% women are at risk of RSA in India. Genetic link is the most important factor responsible for the pathogenesis of RSA. Several genes, such as HLA, FOXP3, MMP and CTLA-4, play crucial roles in this disorder.

Aim: The present study was designed to evaluate the possible association of CTLA-4 with the susceptibility and/or protection to RSA.

Settings and design: A total of 110 subjects (55 RSA cases and 55 controls) were included for this case-control study from the Indian Bengali population, aged between 19 and 35 years.

Materials and methods: Genotyping was carried out by the PCR-RFLP method. The concentration of soluble CTLA-4 (sCTLA-4) was quantified in serum using sandwich ELISA kit.

Statistical analysis used: Genotypic data were statistically analysed using IBM-SPSS (v27), and concentration of sCTLA-4 was determined using Sigma plot (v14). Odds ratios (ORs), 95% confidence intervals and χ ² test were performed for genotyping data, while the t-test was used for sCTLA-4 data. Bonferroni corrected P < 0.05 was considered statistically significant.

Results: The findings revealed an association between CTLA-4 +49A>G variant and reduced risk of RSA under allelic (A versus G: P = 0.049, OR = 0.522), codominant (AA versus AG: P = 0.027, OR = 0.39), dominant (AA versus AG + GG: P = 0.022, OR = 0.379) and over dominant (AG versus AA + GG: P = 0.036, OR = 0.411) inheritance models. However, no significant association was observed between the CTLA-4-1722T>C variant and RSA. Serum sCTLA-4 concentration was significantly lowered in RSA patients as compared to controls (23.82 ± 2.71 ng/ml versus 26.66 ± 3.74 ng/ml, P = 0.0002).

Conclusion: In conclusion, the findings of this preliminary study indicate that the CTLA-4 gene +49A>G (rs231775) variant may contribute to RSA risk in the Indian Bengali population. Further, the finding of reduced sCTLA-4 level suggests the increased risk of RSA. However, further study in a large cohort is warranted to strengthen the findings of the present study.