Abstract |
Hepatic lipase is an enzyme which hydrolyzes triglycerides from plasma lipoproteins and thus takes part in the metabolism of intermediate density lipoproteins and high-density lipoproteins. The search described here concentrated on mutations of the HL gene in 129 patients with combined hypertriglyceridemia/ hyperalphalipoproteinemia and in 184 members of 19 families with familial combined hyperlipidemia. Controls were 100 subjects with favorable lipid values (age 46-51 years). Mutation screening and analysis were performed by temperature-gradient gel electrophoresis, allele-specific restriction genotyping, and sequencing. Six different missense mutations and four different silent mutations were found in the HL gene. The alleles Phe-267 and Gln-343 were detected only once in the patient group with hypertriglyceridemia and hyperalphalipoproteinemia and were not detected in the control group. The allele Met-383 was rare in both patients and controls. We found 9.3% of the patients and only 3.0% of controls to be carrying the Val-73-Met missense mutation. The allele Phe-334 was found in 5.43% of patients and in 2.0% of controls. The difference between the frequencies of these alleles was significant between male patients and male controls (Met-73 P=0.044; Phe-334 P=0.047). Also, the summarized odds ratio of 3.28 (95% confidence interval 1.23-8.73) demonstrates that mutation carriers are significantly more prevalent in the patients. Fifteen carriers of the Met-73 allele were found in six families of the familial combined hyperlipidemia group. Furthermore, six carriers of the Phe-334 allele were found in three families of the same group. In comparison to the controls the summarized odds ratio of 2.45 (95% confidence interval 0.89-6.71) barely missed the level of significance. The linkage between genotype and phenotype was incomplete. These results show an association of the missense mutations Val-73-Met and Leu-334-Phe as susceptibility alleles for combined forms of hyperlipidemia.
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Authors | S Gehrisch, H Kostka, M Tiebel, A Patzak, A Paetzold, U Julius, H E Schroeder, M Hanefeld, W Jaross |
Journal | Journal of molecular medicine (Berlin, Germany)
(J Mol Med (Berl))
Vol. 77
Issue 10
Pg. 728-34
(Oct 1999)
ISSN: 0946-2716 [Print] Germany |
PMID | 10606208
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Adolescent
- Aged
- Aged, 80 and over
- Alleles
- Amino Acid Substitution
- Arteriosclerosis
(etiology, genetics)
- Child
- DNA Mutational Analysis
- Female
- Gene Frequency
- Genetic Predisposition to Disease
- Genotype
- Humans
- Hyperlipidemia, Familial Combined
(complications, enzymology, genetics)
- Hyperlipoproteinemias
(complications, enzymology, genetics)
- Hypertriglyceridemia
(complications, enzymology, genetics)
- Lipase
(deficiency, genetics)
- Lipoproteins, HDL
(blood)
- Liver
(enzymology)
- Male
- Middle Aged
- Phenotype
- Point Mutation
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