The Haplotype TGGAG in the ABCA3 Gene Increases the Risk of Respiratory Distress Syndrome in Preterm Infants in Southern China

Background: Rare mutations in the ATP-binding cassette (ABC) transporter A3 (ABCA3) gene are associated with neonatal respiratory distress syndrome (RDS). The contribution of common single nucleotide polymorphisms (SNPs) to preterm RDS differs between ethnicities and remains unclear in Chinese infants. This study evaluated whether common SNPs and consequent haplotypes increase susceptibility to RDS in a population of preterm infants from the Guangxi Zhuang Autonomous Region of China. Methods: Using a tagging SNP (tSNP) strategy and real-time polymerase chain reaction, we genotyped four tSNPs (i.e., rs150929, rs4787273, rs11867129, and rs17135889) and one coding SNP (p.F353F) of the ABCA3 gene in preterm infants with RDS (n = 83) and without RDS (n = 83). We predicted the haplotypes. Minor allele frequencies (MAFs) and haplotype distributions were compared between the two groups. We analyzed correlations between the clinical data and the genotypes. Results: Seven haplotypes existed at a frequency of 0.01 or greater. The haplotype TGGAG was significantly more frequent in RDS infants than in non-RDS infants (p = 0.026; odds ratio 3.41; 95% confidence interval 1.088-10.685). The MAF of rs17135889 SNP, a crucial SNP of the haplotype TGGAG located in the transcription factor binding site of ABCA3, was significantly higher in RDS infants (p < 0.05); however, the Bonferroni correction test showed no significant difference (p > 0.05). No significant correlation existed between the rs17135889 genotypes (AG/GG) and any clinical characteristic (e.g., oxygen supplementation duration and hospitalization, requirement for ventilation, bronchopulmonary dysplasia complications, and mortality rate). Conclusion: The TGGAG haplotype may be a risk factor for RDS in preterm infants in this Chinese population. Further study is needed with a larger sample size to verify the association between the rs17135889 SNP and increased risk of RDS in preterm infants, and to determine whether rs17135889 can be a reference in further population-based studies of ABCA3. Copyright (C) 2015, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license.