Pei W, Baron H, Müller-Myhsok B, Knoblauch H, Al-Yahyaee S A, Hui R, Wu X, Liu L, Busjahn A, Luft F C, Schuster H
Sino-German Laboratory for Molecular Medicine, Fu Wai Heart Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences.
Clin Genet. 2000 Jan;57(1):29-34. doi: 10.1034/j.1399-0004.2000.570105.x.
We examined familial combined hyperlipidemia (FCHL) families from nonisolated 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 German families with 137 members, 92 of whom met the criteria of affected in terms of the low density lipoprotein (LDL) and triglyceride levels in excess of the 90th percentile for age and gender. In China, we recruited 12 families 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. Two-point linkage analysis allowing for heterogeneity gave a maximum linkage of disorder score (HLOD) of 2.60 right over D1S194, estimating the proportion of linked families at 36%. This marker is adjacent to D1S104. The evidence for linkage was roughly the same both in the German (HLOD 1.40) and Chinese 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 an earlier twin study from our laboratory. We interpret our observations as encouraging support for the recent findings indicating the presence of a gene for FCHL on chromosome 1q. Furthermore, since DIS194 is adjacent to the gene for the RXR, we suggest that RXR is an attractive candidate for involvement in FCHL.
我们研究了来自德国和中国非隔离地区的家族性混合型高脂血症（FCHL）家族，以确定在更广泛的人群中是否能证实对1号染色体上FCHL基因座的支持。我们招募了24个德国家族，共137名成员，其中92名成员根据年龄和性别的低密度脂蛋白（LDL）和甘油三酯水平超过第90百分位数符合患病标准。在中国，我们招募了12个家族，共81名成员。所有患病者的总胆固醇浓度>240mg/dl，甘油三酯浓度>250mg/dl。我们检测了APOA2、D1S1677、D1S104、D1S194、D1S426和D1S196这些标记物。考虑到异质性的两点连锁分析得出，在D1S194上的疾病得分（HLOD）最大连锁值为2.60，估计连锁家族比例为36%。该标记物与D1S104相邻。在德国家族（HLOD 1.40）和中国家族（HLOD 1.52）中，连锁证据大致相同。标记物D1S194靠近视黄酸X受体（RXR）基因座，在我们实验室早期的一项双胞胎研究中发现该基因座与甘油三酯水平相关。我们将我们的观察结果解释为对最近研究结果的有力支持，这些结果表明1号染色体上存在FCHL基因。此外，由于DIS194与RXR基因相邻，我们认为RXR是参与FCHL的一个有吸引力的候选基因。
