TY - JOUR
T1 - Genetic contribution to factor VII levels in families of patients undergoing coronary arteriography
AU - Jee, S. H.
AU - Song, K. S.
AU - Shim, W.
AU - Kim, H. K.
AU - Suh, I.
AU - Yoon, Y.
AU - Beaty, T. H.
PY - 2002
Y1 - 2002
N2 - An elevated plasma level of factor VII is a risk factor for coronary artery disease. We investigated environmental, familial, and genetic influences on factor VII activity in 508 family members of 87 probands who underwent elective coronary arteriography. Maximum likelihood methods were used to fit several genetic and non-genetic models of inheritance to these data to determine whether an unobserved Mendelian major gene could explain the familial distribution of factor VII. Factor VII activities were adjusted for age, gender, body mass index, smoking, alcohol consumption, menopause status, and triglycerides prior to this segregation analysis (this model accounted for 33.5% of the total variation). Adjusted factor VII activities showed strong familial aggregation with an estimated parent-offspring correlation of 0.34, sibling correlation of 0.36 and a smaller spouse correlation of 0.16. Regressive models were used to test genetic and non-genetic models in these 87 families. Mendelian single-locus models with either two or three underlying genotypic distributions of factor VII activities were best supported by these data. Essentially, these Mendelian models suggest most individuals come from a low distribution (mean, 116%), with a few individuals homozygous for a high allele drawn from a distribution with a mean of 166%. Future linkage studies may be worthwhile to further clarify the mechanisms controlling factor VII activity.
AB - An elevated plasma level of factor VII is a risk factor for coronary artery disease. We investigated environmental, familial, and genetic influences on factor VII activity in 508 family members of 87 probands who underwent elective coronary arteriography. Maximum likelihood methods were used to fit several genetic and non-genetic models of inheritance to these data to determine whether an unobserved Mendelian major gene could explain the familial distribution of factor VII. Factor VII activities were adjusted for age, gender, body mass index, smoking, alcohol consumption, menopause status, and triglycerides prior to this segregation analysis (this model accounted for 33.5% of the total variation). Adjusted factor VII activities showed strong familial aggregation with an estimated parent-offspring correlation of 0.34, sibling correlation of 0.36 and a smaller spouse correlation of 0.16. Regressive models were used to test genetic and non-genetic models in these 87 families. Mendelian single-locus models with either two or three underlying genotypic distributions of factor VII activities were best supported by these data. Essentially, these Mendelian models suggest most individuals come from a low distribution (mean, 116%), with a few individuals homozygous for a high allele drawn from a distribution with a mean of 166%. Future linkage studies may be worthwhile to further clarify the mechanisms controlling factor VII activity.
KW - Factor VII activity
KW - Segregation analysis
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U2 - 10.1097/00001721-200201000-00004
DO - 10.1097/00001721-200201000-00004
M3 - Article
C2 - 11994564
AN - SCOPUS:0036234524
SN - 0957-5235
VL - 13
SP - 25
EP - 33
JO - Blood Coagulation and Fibrinolysis
JF - Blood Coagulation and Fibrinolysis
IS - 1
ER -