Locus for quantitative HDL-cholesterol on chromosome 10q in Finnish families with dyslipidemia.
Decreased HDL-cholesterol (HDL-C) and familial combined hyperlipidemia (FCHL) are the two most common familial dyslipidemias predisposing to premature coronary heart disease (CHD). These dyslipidemias share many phenotypic features, suggesting a partially overlapping molecular pathogenesis. This was supported by our previous pooled data analysis of the genome scans for low HDL-C and FCHL, which identified three shared chromosomal regions for a qualitative HDL-C trait on 8q23.1, 16q23.3, and 20q13.32. This study further investigates these regions as well as two other loci we identified earlier for premature CHD on 2q31 and Xq24 and a locus for high serum triglycerides (TGs) on 10q11. We analyzed 67 microsatellite markers in an extended study sample of 1,109 individuals from 92 low HDL-C or FCHL families using both qualitative and quantitative lipid phenotypes. These analyses provided evidence for linkage (a logarithm of odds score of 3.2) on 10q11 using a quantitative HDL-C trait. Importantly, this region, previously linked to TGs, body mass index, and obesity, provided evidence for association for quantitative TGs (P = 0.0006) and for a combined trait of HDL-C and TGs (P = 0.008) with marker D10S546. Suggestive evidence for linkage also emerged for HDL-C on 2q31 and for TGs on 20q13.32. Finnish families ascertained for dyslipidemias thus suggest that 10q11, 2q31, and 20q13.32 harbor loci for HDL-C and TGs.
Lilja
Heidi E
HE
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland.
Suviolahti
Elina
E
Soro-Paavonen
Aino
A
Hiekkalinna
Tero
T
Day
Aaron
A
Lange
Kenneth
K
Sobel
Eric
E
Taskinen
Marja-Riitta
MR
Peltonen
Leena
L
Perola
Markus
M
Pajukanta
Päivi
P
D000328:Adult; D000368:Aged; D008076:Cholesterol, HDL / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D002889:Chromosomes, Human, Pair 2; D002890:Chromosomes, Human, Pair 20; D005192:Family Health; D005387:Finland / Q000453:epidemiology; D008040:Genetic Linkage; D006801:Humans; D006949:Hyperlipidemias / Q000145:classification / Q000209:etiology / Q000235:genetics*; D018895:Microsatellite Repeats; D008875:Middle Aged; D017720:Molecular Epidemiology
D008076:Cholesterol, HDL