Placental CCR5 polymorphisms in relation to fetal growth

Area of Science:

• Reproductive Biology
• Immunology
• Genetics

Background:

• The placenta is crucial for fetal growth, with immune interactions influencing its development and function.
• The CCR5 gene encodes a pro-inflammatory receptor found in the placenta, but its role in fetal growth and placental DNA methylation is understudied.

Purpose of the Study:

• To investigate the association between CCR5 gene polymorphisms and birth outcomes.
• To explore the impact of CCR5 variants on placental DNA methylation, particularly in the context of infection.

Main Methods:

• Assessed two functional CCR5 polymorphisms (Δ32 deletion and rs1799987 A/G promoter mutation) in the EPIC cohort (n=233).
• Validated rs1799987 association with birth weight using the NICHD dataset (n=286).
• Examined CCR5 variants and DNA methylation in the CARMA-Preg cohort (n=200), enriched for HIV exposure.

Main Results:

• Variant alleles in CCR5 were associated with birth weight in the EPIC cohort (p=0.007 and p=0.01).
• The association of rs1799987 with birth weight was validated in the NICHD dataset (p=0.003).
• These associations were not present in the HIV-exposed CARMA-Preg cohort. rs1799987 was linked to altered DNA methylation across a large region including CCR2 and CCR5, but this methylation was not associated with birth weight.

Conclusions:

• CCR5 gene variants show potential associations with fetal growth, influencing birth weight in specific populations.
• The absence of association in HIV-exposed pregnancies suggests context-dependent effects.
• Further studies are required to confirm these findings, considering population structure and haplotype complexities to establish causality.