Genome-wide Significance and Replication of the Ch... [Circ Cardiovasc Genet. 2011] - PubMed result

Genome-wide Significance and Replication of the Ch... [Circ Cardiovasc Genet. 2011] - PubMed result: "Circ Cardiovasc Genet. 2011 Jun 10. [Epub ahead of print]
Genome-wide Significance and Replication of the Chromosome 12p11.22 Locus Near the PTHLH Gene for Peripartum Cardiomyopathy.
Horne BD, Rasmusson KD, Alharethi R, Budge D, Brunisholz KD, Metz T, Carlquist JF, Connolly JJ, Porter TF, Lappé DL, Muhlestein JB, Silver R, Stehlik J, Park JJ, May HT, Bair TL, Anderson JL, Renlund DG, Kfoury AG.
Source
1 Intermountain Medical Center & University of Utah, Salt Lake City, UT;

Abstract
BACKGROUND:
-Peripartum (PP) cardiomyopathy (CM) is a rare condition of unknown etiology that occurs in late pregnancy or early postpartum. Initial evidence suggests that genetic factors may influence PPCM. This study evaluated and replicated genome-wide association of single nucleotide polymorphisms (SNPs) with PPCM.

METHODS AND RESULTS:
-Genome-wide SNPs in females with verified PPCM diagnosis (n=41) were compared separately to Local Controls (n=49 post-menopausal age-discordant females with parity ≥1 and no heart failure) and iControls (n=654 females aged 30-84 with unknown phenotypes). A replication study of independent population samples utilized new cases (PPCM2, n=30) compared to new age-discordant controls (Local2, n=124) and to younger controls (YC, n=89) and obstetrical controls (OBC, n=90). A third case set of pregnancy-associated (PA) CM cases not meeting strict PPCM definitions (n=29) was also studied. In the genome-wide association study, one SNP (rs258415) met genome-wide significance for PPCM vs. Local Controls (p=2.06 x 10(-8), OR=5.96). This was verified vs. iControls (p=7.92 x 10(-19), OR=8.52). In the replication study for PPCM2 cases, rs258415 (ORs are per C allele) replicated at p=0.009 vs. Local2 Controls (OR=2.26). This replication was verified for PPCM2 vs. YC (p=0.029, OR=2.15) and vs. OBC (p=0.013, OR=2.44). In PACM cases, rs258415 had a similar effect vs. Local2 Controls (p=0.06, OR=1.79), YC (p=0.14, OR=1.65), and OBC (p=0.038, OR=1.99).

CONCLUSIONS:
-Genome-wide association with PPCM was discovered and replicated for rs258415 at chromosome 12p11.22 near PTHLH. This study indicates a role of genetic factors in PPCM and provides a new locus for further pathophysiological and clinical investigation.

PMID:
21665988
[PubMed - as supplied by publisher]

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