Abstract 16347: Peripartum Cardiomyopathy-Associated Sequence Variant at the PTHLH Locus is Not Predictive of Idiopathic or Ischemic Cardiomyopathy
Background: A rare diagnosis with undescribed etiology, Peripartum (PP) cardiomyopathy (CM) occurs near the end of pregnancy or during the early postpartum period. A single nucleotide polymorphism (SNP) at the PTHLH locus (rs258415) was previously discovered by GWAS and independently validated to predict PPCM. Whether this SNP is associated with other forms of CM is unclear, thus this study evaluated the association of rs258415 with idiopathic (ID) CM and ischemic CM compared to PPCM.
Methods: Allele frequencies among patients with IDCM (n=381) and ischemic CM (n=269) were compared to PPCM patients (n=30) previously evaluated in a replication study of the SNP. Bonferroni-corrected significance (p≤0.025) was used for the two CM phenotype comparisons to PPCM. PPCM phenotype was defined using clinical parameters or (in their absence) medical records, while IDCM and ischemic CM phenotypes required both ICD-9 codes and clinical documentation of the etiology. Secondary analyses compared the IDCM and ischemic CM phenotypes to multiple set of non-CM controls used in previous PPCM studies: iControls (n=654 females aged 30-84 with unknown phenotypes), older controls (OC: age>70 years, n=124), and young controls (YC: age 20-44, n=89).
Results: The variant C allele was present in 31.7% of PPCM patients compared to 18.8% of IDCM (odds ratio [OR]=2.01, 95% CI: 1.13, 3.57; p=0.018) and 19.2% of ischemic CM (OR=1.96, 95% CI: 1.11, 3.44; p=0.020). All PPCM patients were female, while 29% of IDCM and 14% of ischemic CM were female. No differences in the frequency of the C allele existed, however, between females and males for patients with IDCM (16.5% vs. 19.7%; p=0.38) or ischemic CM (25.5% vs. 18.1%; p=0.07). Compared to all three control sets, frequency of the C allele was not different for IDCM (all p≥0.30) or ischemic CM (all p>0.22).
Conclusions: The frequency of the variant C allele at rs258415 was significantly higher for PPCM patients compared to IDCM or ischemic CM patients. However, no differences in rs258415 C allele frequency were found for IDCM or ischemic CM compared to three non-CM control sets. This genetic evidence suggests that PPCM may be of distinct etiology than is IDCM or ischemic CM.
- © 2011 by American Heart Association, Inc.