# Club cell secretory protein (CC16) polymorphisms in preterm neonates with respiratory distress syndrome and bronchopulmonary dysplasia

## TL;DR

This study found that certain genetic variations in the CC16 protein are linked to a higher risk of respiratory distress in preterm babies.

## Contribution

The study identifies specific CC16 polymorphisms (rs4963506 and rs12270961) associated with increased risk of respiratory distress syndrome in preterm neonates.

## Key findings

- The GG rs4963506 and GG rs12270961 CC16 variants are linked to higher risk of respiratory distress syndrome in preterm neonates.
- The GG rs4963506 variant is associated with elevated serum CC16 levels on the first postnatal day.
- No association was found between CC16 polymorphisms and bronchopulmonary dysplasia.

## Abstract

To investigate the genotype frequencies of club cell secretory protein (CC16) polymorphisms in preterm neonates and explore their association with respiratory distress syndrome (RDS), and bronchopulmonary dysplasia (BPD). A prospective cohort study was conducted including 187 preterm neonates of ≤ 34 weeks of gestational age. Genotype frequencies of rs4963506, rs12270961, and rs3741240 CC16 polymorphisms were detected, comparing the CC16 polymorphisms between neonates with versus without RDS, and with versus without BPD. Serum CC16 was measured, when available, on the first and fourteenth postnatal days. A significant association of increased risk of RDS was detected for the homozygous GG rs4963506 variant (OR 3.03, 95%CI 1.36–6.75, p = 0.021), and the homozygous GG rs12270961 variant (OR 2.88, 95%CI 1.31–6.28, p = 0.024), but not for the homozygous GG rs3741240 variant, after adjusting for gestational age, mode of delivery, and antenatal administration of steroids. The homozygous GG rs4963506 variant was also associated with higher serum levels of CC16 compared to the GA/AA rs4963506 variants, on the first postnatal day. No associations between BPD and the genotype frequencies of any polymorphisms were detected. Conclusion: In preterm neonates, the homozygous GG rs4963506 and rs12270961 variants were both substantially associated with a higher risk of RDS. Further studies are warranted to validate our findings and explore the potential role of CC16 polymorphism detection in neonates at risk of respiratory morbidities.
What is Known:∙ Serum club cell secretory protein (CC16) reflects the lung’s developmental maturation and healing mechanisms for tissue damage.∙ The CC16 polymorphisms have been inconsistently associated with lung function in children.∙ No evidence exists regarding the association between CC16 polymorphisms and respiratory morbidity in neonates.What is new:∙ Homozygous GG rs4963506 and GG rs12270961variants were associated with increased risk of respiratory distress in neonates.∙ Homozygous GG rs4963506 variant was also associated with higher serum levels of CC16 on the first postnatal day.∙ No associations between BPD and the genotype frequencies of any polymorphisms were detected.

What is Known:

∙ Serum club cell secretory protein (CC16) reflects the lung’s developmental maturation and healing mechanisms for tissue damage.

∙ The CC16 polymorphisms have been inconsistently associated with lung function in children.

∙ No evidence exists regarding the association between CC16 polymorphisms and respiratory morbidity in neonates.

What is new:

∙ Homozygous GG rs4963506 and GG rs12270961variants were associated with increased risk of respiratory distress in neonates.

∙ Homozygous GG rs4963506 variant was also associated with higher serum levels of CC16 on the first postnatal day.

∙ No associations between BPD and the genotype frequencies of any polymorphisms were detected.

The online version contains supplementary material available at 10.1007/s00431-025-06169-7.