Support for linkage of familial combined hyperlipidemia to chromosome 1q21-q23 in Chinese and German families

We examined familial combined hyperlipidemia (FCHL) families from nonisolat ed regions in Germany and China to see if we could corroborate support for a chromosome 1q FCHL locus in more general populations. We recruited 24 Ger man families with 137 members, 92 of whom met the criteria of affected in t erms of the low density lipoprotein (LDL) and triglyceride levels in excess of the 90th percentile for age and gender. In China, we recruited 12 famil ies with a total of 81 members. All affected persons had total cholesterol concentrations > 240 mg/dl and triglyceride concentrations > 250 mg/dl. We examined the markers APOA2, D1S1677, D1S104, D1S194, D1S426, and D1S196. Tw o-point linkage analysis allowing for heterogeneity gave a maximum linkage of disorder score (HLOD) of 2.60 right over D1S194, estimating the proporti on of linked families at 36%. This marker is adjacent to D1S104. The eviden ce for linkage was roughly the same both in the German (HLOD 1.40) and Chin ese families (HLOD 1.52). Marker D1S194 is close to the retinoid X receptor (RXR) gene locus, which was found to be linked to triglyceride levels in a n earlier twin study from our laboratory. We interpret our observations as encouraging support for the recent findings indicating the presence of a ge ne for FCHL on chromosome 1q. Furthermore, since D1S194 is adjacent to the gene for the RXR, we suggest that RXR is an attractive candidate for involv ement in FCHL.