出版社：American Society for Biochemistry and Molecular Biology
摘要：Previous studies have demonstrated that low density lipoproteincholesterol (LDL-C) concentration is influenced by both genesand environment. Although rare genetic variants associated withMendelian causes of increased LDL-C are known, only one commongenetic variant has been identified, the apolipoprotein E gene(APOE). In an attempt to localize quantitative trait loci (QTLs)influencing LDL-C, we conducted a genome-wide linkage scan ofLDL-C in participants of the Strong Heart Family Study (SHFS).Nine hundred eighty men and women, age 18 years or older, in32 extended families at three centers (in Arizona, Oklahoma,and North and South Dakota) were phenotyped for LDL-C concentrationand other risk factors. Using a variance component approachand the program SOLAR, and after accounting for the effectsof covariates, we detected a QTL influencing LDL-C on chromosome19, nearest marker D19S888 at 19q13.41 [logarithm of odds (LOD)= 4.3] in the sample from the Dakotas. This region on chromosome19 includes many possible candidate genes, including the APOE/C1/C4/C2gene cluster. In follow-up association analyses, no significantevidence for an association was detected with the APOE*2 andAPOE*4 alleles (P = 0.76 and P = 0.53, respectively). Suggestiveevidence of linkage to LDL-C was detected on chromosomes 3q,4q, 7p, 9q, 10p, 14q, and 17q. These linkage signals overlappositive findings for lipid-related traits and harbor plausiblecandidate genes for LDL-C.Supplementary key words genetics • lipids • low density lipoprotein
2 and APOE*
