全周 (9AM - 6PM)

我们和你在一起

Extra info thumb
HYPOALPHALIPOPROTEINEMIA, PRIMARY, 1

HYPOALPHALIPOPROTEINEMIA, PRIMARY, 1

Alternative titles; symbolsHYPOALPHALIPOPROTEINEMIA, FAMILIAL; FHAHIGH DENSITY LIPOPROTEIN DEFICIENCY; HDLDFAMILIAL HDL DEFICIENCY; FHDHDL CHOLESTEROL, LOW SERUM...

Alternative titles; symbols

  • HYPOALPHALIPOPROTEINEMIA, FAMILIAL; FHA
  • HIGH DENSITY LIPOPROTEIN DEFICIENCY; HDLD
  • FAMILIAL HDL DEFICIENCY; FHD
  • HDL CHOLESTEROL, LOW SERUM; HDLC

Other entities represented in this entry:

  • HIGH DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 13, INCLUDED; HDLCQ13, INCLUDED

▼ Description
Twenty to 30% of early familial coronary heart disease (CHD) is ascribed to hypoalphalipoproteinemia, or high density lipoprotein deficiency. Although not initially recognized as a predisposing dyslipidemia, extensive epidemiologic work has implicated low high-density lipoprotein cholesterol (HDLC) levels in increased risk of cardiovascular disease, and low HDLC is considered to be a true dyslipidemic syndrome (Warnick and Wood, 1995).

Genetic Heterogeneity of Primary Hypoalphalipoproteinemia

Primary hypoalphalipoproteinemia-2 (618463) is caused by mutation in the APOA1 gene (107680) on chromosome 11q23.

▼ Clinical Features
As in Tangier disease, an autosomal recessive disorder, the dominantly inherited disorder familial hypoalphalipoproteinemia shows a reduction in cellular cholesterol efflux (Marcil et al., 1999).

Clee et al. (2000) examined the phenotypes of 77 individuals heterozygous for mutations in the ABC1 gene. Heterozygotes had an approximately 40 to 45% decrease in HDL cholesterol (HDL-C) and apo-AI and a mild (approximately 10%) decrease in apo-AII compared with unaffected family members. Mean triglycerides were increased by approximately 40% in heterozygotes compared with unaffected family members. There was no significant decrease in total cholesterol or LDL cholesterol in heterozygotes. Symptomatic vascular disease was over 3 times as frequent in adult heterozygotes as in unaffected family members. The mean age of CAD onset was on average a decade earlier in heterozygotes compared to the unaffected controls. Age is an important modifier of the phenotype in heterozygotes, as a significantly larger percentage of individuals aged 30 to 70 years had HDL-C less than the fifth percentile compared to those younger than 30 years (p = 0.004).

▼ Mapping
After demonstrating mutations in the ABC1 gene in patients with Tangier disease, Brooks-Wilson et al. (1999) studied 4 French Canadian families with familial hypoalphalipoproteinemia. Linkage analysis revealed a maximum lod score of 9.67 at a recombination fraction of 0.0 at D9S277, the region to which Tangier disease had been mapped. These 2 diseases had hitherto been considered distinct, with different clinical and biochemical characteristics.

▼ Molecular Genetics
In affected members of French Canadian families with hypoalphalipoproteinemia, Brooks-Wilson et al. (1999) identified heterozygous mutations in the ABC1 gene (600046.0001-600046.0004). One of the families had previously been studied by Marcil et al. (1995).

Tags: 9q31.1