title: Mutations of the human hepatic lipase gene in patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in patients with familial combined hyperlipidemia.
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.
authors.affiliation: Institut für Klinische Chemie und Laboratoriumsmedizin, Medizinische Fakultät TU Dresden, Germany. gehrisch@rcs.urz.tu-dresden.de
authors.forename: S
authors.initials: S
authors.lastname: Gehrisch
authors.forename: H
authors.initials: H
authors.lastname: Kostka
authors.forename: M
authors.initials: M
authors.lastname: Tiebel
authors.forename: A
authors.initials: A
authors.lastname: Patzak
authors.forename: A
authors.initials: A
authors.lastname: Paetzold
authors.forename: U
authors.initials: U
authors.lastname: Julius
authors.forename: H E
authors.initials: HE
authors.lastname: Schroeder
authors.forename: M
authors.initials: M
authors.lastname: Hanefeld
authors.forename: W
authors.initials: W
authors.lastname: Jaross
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D006951:Hyperlipoproteinemias / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D015228:Hypertriglyceridemia / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D008049:Lipase / Q000172:deficiency / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation
chemical_list: D008075:Lipoproteins, HDL; D008049:Lipase