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Korean Journal of Epidemiology 1999;21(2): 176-184.
A Study of Major Gene Dominant Family for Factor VII Concentration: Segregation Analysis.
Sun Ha Jee, Kyung Sooon Song, Won Heum Shim, Il Suh, Hyun Kyung Kim, Young Sup Yoon, Eunna Go, Jung Yong Park, Miyang Kim, Sujeong Kim
1Graduate School of Health Science and Management.
2Department of Clinical Pathology, College of Medicine,Yonsei University, Seoul, Korea.
3Internal Medicine, College of Medicine, Yonsei University,Seoul, Korea.
4Preventive Medicine, College of Medicine, Yonsei University,Seoul, Korea.
Abstract
Elevated plasma level of factor VII is a risk factor for coronary artery disease. We investigated environmental, familial, and genetic influences on factor VII levels. We used maximum likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance to the data to determine whether Mendelian inheritance of a major gene could best explain the familial distribution of factor VII. The study population included 414 family members of 67 subjects who had undergone elective coronary arteriography. The factor VII level was adjusted for age, gender, body mass index, smoking and alcohol drinking (R2=20.6%). Factor VII levels revealed strong familial aggregation with estimated correlation spouse of 0.12, parent-offspring of 0.31, and siblings of 0.40. Regressive models were used to examine inter-individual variation in adjusted factor VII levels in these 67 families. This analysis strongly favored a major gene model with codominant transmission. Genotypic means were 111.6, 123.2, and 184.3% with relative frequencies of 59.4%, 35.4%, and 5.2%. This putative major gene explains 39.9% of the total variance of factor VII. Likelihood was used to search for etiologic heterogeneity by sorting pedigrees into groups that favor one model over another. Compared to pedigrees less favoring Mendelian models, pedigrees favoring Mendelian codominant models have almost 8 times earlier onset of coronary heart disease. These family data suggest that there are strong familial and genetic effects on the factor VII activity in these high risk families. Therefore, linkage studies in these families may be worthwhile to clarify the molecular basis of factor VII levels.
Keywords: Factor VII activity; segregation; Major gene; Gene dominant family score
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