Elucidation of an underlying etiology of atherogenic type IV hyperlipoproteinemia and development of its genetic diagnostic method

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We have systematically investigated an underlying etiology of primary type IV hyperlipoproteinemia by monitoring LPL immunoreactive mass in postheparin plasma of 32 non diabetic patients with primary type IV hyperlipoproteinemia using our sandwich-EIA technique for the first screening, follwed by a second screening for LPL gene aberrations using PCR-SSCP and direct sequencing methods improved by us. By this approach, we found that 24 patients (75% of the tested patients) had low LPL mass values (51-129 ng/ml) which is lower than the 5th percentile of control LPL mass values. Of the 24 patients, 18 were available for analyzing LPL gene aberrations. We found 14 patients had LPL aberrations in heterozygous state. Thus heterozygous LPL deficiency is an underlying genetic disorder of primary type IV hyperlipoproteinemia. The five common polymorphisms (HindIII,HinfI,MaeII,PvuII and tetrarepeat) on LPL gene and haplotypes which were constructed with the five common polymorphisms did not affect LPL mass values. Subjects whose LPL mass level is lower than 5th percentile are prone to manifest type IV hyperlipoproteinemia when this is coupled with triglyceride synthesis stimulating factors like high alcohol intake. The measurement of plasma LPL mass levels and/or early diagnosis of heterozygous LPL deficiency will help to prevent the manifestation of type IV hyperlipoproteinemiain old age, if the subjects improve lifestyle as well as superimposing triglyceride synthesisstimulating factors.