MOLECULAR GENETICS OF CHOLESTEROL METABOLIC PATHWAY AND TREATMENT OF ATHEROSCLEEROSIS

家族性高胆固醇血症中的ldl受体异常。世界上已经报道了600多种不同的LDL受体基因突变。我们收集了20个FH纯合子和1500多个FH杂合子。在我们的实验室已经鉴定了11种LDL受体基因变异。低密度脂蛋白受体基因K790X突变是本区常见突变，FH患者中K790X突变的发生率为20.9%。这11个突变体仅占FH的38.8%，在其他61.2%的FH中，LDL受体基因突变体尚不清楚。低脂蛋白血症中微粒体转移蛋白（mtp）基因突变。先证者为男性，29岁，CHOL为33 mg/dl， TG为0 mg/dl， HDL-C为28 mg/dl。基因分析显示，10号外显子和9号内含子连接处（G到a）发生点突变，导致剪接异常，无MTP蛋白。先证者在4q染色体上只有他母亲的基因。母体同位体是该患者MTP基因突变纯合性的基础。唐吉氏病的Abc1突变。丹吉尔病是一种罕见的疾病，其特征是高密度脂蛋白胆固醇水平极低，橙色扁桃体肥大，动脉粥样硬化和脊髓病变。日本报告的丹吉尔病患者不到10例。1999年，ABC1突变被发现是丹吉尔病的致病基因突变。我们在这3例Tangie病中发现了3个新的ABC1基因突变。突变为18外显子的A2743C和N875H突变。

LDL-RECEPTOR ABNORMALITIES IN FAMILIAL HYPERCHOLESTEROLEMIA.More than 600 different mutations in the LDL receptor gene have been reported in the world. We have collected 20 homozygotes and more than 1,500 heterozygotes of FH. Eleven variants of LDL receptor gene have been identified in our laboratory. K790X mutant of LDL-receptor gene was a common mutant in this district, and the frequency was 20,9% in FH patients. These 11 mutants accounted for only 38.8% of FH and in other 61.2% of FH the LDL receptor gene mutants remained unknown.MICROSOMAL TRANSFER PROTEIN (MTP) GENE MUTATION IN ABETALIPOPROTEINEMIA.The proband was 29 male patient, and his CHOL level was 33 mg/dl, TG was 0 mg/dl, and HDL-C was 28 mg/dl. The gene analysis showed a point mutation in the junction of exon 10 and intron 9 (G to A), which would produce splicing abnormalities and no MTP protein. The proband had only his mother's genes in chromosome 4q. Maternal isodisomy was the basis for homozygosity of the MTP gene mutatin in this patient.ABC1 MUTATION IN TANGIE'S DISEASE.Tangier's disease is a rare disease characterized by very low levels of HDL-cholesterol, hypertrophy of orange-coloured tonsils, atherosclerosis and poluneuropathy. Less than 10 patients of Tangier's disease have been reported in Japan. In 1999, ABC1 mutations have been found to be a causative gene mutation in Tangier's disease. We found three novel mutations of ABC1 gene in our three Tangie's disease. Their mutation were A2743C and N875H mutation in exon 18.