Segregation Analysis of Serum LDL-cholesterol in Korean Families of Coronary Heart Disease Patients

Park, Jung Yong; Jee, Sun Ha; Song, Kyung Soon; Shim, Won Heum; Kim, Soo Jeong

Abstract

PURPOSES: The aim of this study was to investigate the familial correlation of lipid profile and the mode of inheritance of LDL-cholesterol through segregation analysis. The study population included 414 family members of 67 Probands who had a coronary heart disease.
METHODS
Gene frequency(qH) of the allele for high LDL-cholesterol levels, means of each genotypes, and other putative gene related parameters were estimated. Maximum likelihood methods were used to fit several genetic and nongenetic modes of inheritance to these data to determine if an unobserved Mendelian major gene could explain the familial distribution of LDL-cholesterol. LDL-cholesterol levels were adjusted for age, gender, body mass index, smoking and alcohol consumption.
RESULTS
LDL-cholesterol levels revealed familial correlation among spouses, parent-offsprings and siblings with correlations of 0.10, 0.22, and 0.32, respectively. The heritability of LDL-cholesterol was 53%. Two models of inheritance in LDL-cholesterol distribution, the Mendelian codominant model and the polygenic equal transmission model were found. Comparison of these two models in each family among 67 families showed that thiry-six families favored the major gene model with Mendelian codominant and thirty-one families favored the polygenic model of equal transmission. In families favoring Mendelian codominant inheritance, means of each genotypes; LL, HL, HH were 102.1, 143.3, 248.4 mg/dl and gene frequency of H allele was 0.08. In families favoring equal transmission inheritance, means of each genotypes were 101.6, 122.7, 185.5 mg/dl and gene frequency of H allele was 0.14.
CONCLUSIONS
In conclusion, families of coronary heart disease patients of this study showed substantial familial correlation and results suggested that variation in LDL-cholesterol may be influenced by major gene effect.