TY - JOUR
T1 - Association of an intronic, but not any exonic, FRMD4B sequence variant and heart failure
AU - Matkovich, Scot J.
AU - Van Booven, Derek J.
AU - Cappola, Thomas P.
AU - Dorn, Gerald W.
PY - 2010/8
Y1 - 2010/8
N2 - Common forms of heart failure (HF) exhibit familial clustering, but specific genetic risk factors have been challenging to identify. A recent single-nucleotide polymorphism (SNP) microarray study implicated a locus within an intron of FRMD4B in Caucasian HF. Here, we used next-generation resequencing of pooled DNA and individual Sequenom genotyping to test for associations between FRMD4B SNPs and ischemic and/or nonischemic cardiomyopathy in two independent populations. Exonic resequencing of Caucasians and African-Americans identified 32 FRMD4B SNPs, 13 of which had allele frequencies greater than 1%. None of these common FRMD4B SNPs were significantly associated with ischemic, nonischemic, or all-cause HF in either of the study populations. We individually genotyped the seminal intronic rs6787362 FRMD4B SNP in the primary study population and compared genotypes between HF cases and controls. The rs6787362 variant allele was more frequent in Caucasians with ischemic cardiomyopathy, and carriers (heterozygous or homozygous) of the variant allele had increased risk of HF (OR 1.437, CI 1.085-1.904; p= 0.0118). No such association was seen for African-American HF. These results confirm an association between the intronic rs6787362 FRMD4B SNP and ischemic cardiomyopathy in a European-derived population, but do not support the proposition that coding FRMD4B variants are susceptibility factors in common HF.
AB - Common forms of heart failure (HF) exhibit familial clustering, but specific genetic risk factors have been challenging to identify. A recent single-nucleotide polymorphism (SNP) microarray study implicated a locus within an intron of FRMD4B in Caucasian HF. Here, we used next-generation resequencing of pooled DNA and individual Sequenom genotyping to test for associations between FRMD4B SNPs and ischemic and/or nonischemic cardiomyopathy in two independent populations. Exonic resequencing of Caucasians and African-Americans identified 32 FRMD4B SNPs, 13 of which had allele frequencies greater than 1%. None of these common FRMD4B SNPs were significantly associated with ischemic, nonischemic, or all-cause HF in either of the study populations. We individually genotyped the seminal intronic rs6787362 FRMD4B SNP in the primary study population and compared genotypes between HF cases and controls. The rs6787362 variant allele was more frequent in Caucasians with ischemic cardiomyopathy, and carriers (heterozygous or homozygous) of the variant allele had increased risk of HF (OR 1.437, CI 1.085-1.904; p= 0.0118). No such association was seen for African-American HF. These results confirm an association between the intronic rs6787362 FRMD4B SNP and ischemic cardiomyopathy in a European-derived population, but do not support the proposition that coding FRMD4B variants are susceptibility factors in common HF.
KW - Cardiomyopathy
KW - Heart failure
KW - Molecular genetics
UR - http://www.scopus.com/inward/record.url?scp=77955767759&partnerID=8YFLogxK
U2 - 10.1111/j.1752-8062.2010.00220.x
DO - 10.1111/j.1752-8062.2010.00220.x
M3 - Article
C2 - 20718813
AN - SCOPUS:77955767759
SN - 1752-8054
VL - 3
SP - 134
EP - 139
JO - Clinical and translational science
JF - Clinical and translational science
IS - 4
ER -