Article

Association of lipoprotein lipase gene variation with the physiological components of the insulin-resistance syndrome in the population of the San Luis Valley, Colorado.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15261.
Diabetes Care (impact factor: 8.09). 12/1993; 16(11):1502-6. pp.1502-6
Source: PubMed

ABSTRACT To cross-sectionally evaluate the presence of clustering of the insulin-resistance syndrome components. Tests were conducted for association of the HindIII restriction site polymorphism at the lipoprotein lipase locus with clustering of the physiological components of the insulin resistance syndrome.
DNA samples of 370 normoglycemic Hispanics and 520 normoglycemic non-Hispanic whites from the San Luis Valley, Colorado, were amplified by the polymerase chain reaction. Lipids and glucose were determined by the standard procedures. Cross-tabulation and chi 2 analysis were used.
The insulin-resistance syndrome components (elevated fasting insulin, reduced high-density lipoprotein cholesterol, and elevated triglycerides) appeared together in individuals of this population sample more often than expected by chance. Individuals in the population with the (+/+) lipoprotein lipase-HindIII restriction of fragment-length polymorphism genotype were more likely to have elevated fasting insulin and triglycerides and a reduced high-density lipoprotein-cholesterol level than subjects with the (+/-) genotype (odds ratio = 2.3, 95% confidence interval 1.38-3.98).
As expected from the physiological function of lipoprotein lipase, the primary association of lipoprotein lipase genotypes is with triglyceride and high-density lipoprotein-cholesterol levels. This appears to be the first reported genetic association with the insulin-resistance syndrome and may reflect genotype specific differences in the regulation of lipoprotein lipase by insulin.

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    Article: Genetic variation at the lipoprotein lipase locus and plasma lipoprotein and insulin levels in the Québec Family Study.
    O Ukkola, C Garenc, L Pérusse, J Bergeron, J P Després, D C Rao, C Bouchard
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    ABSTRACT: The associations between the S447X, BamHI, HindIII and PvuII DNA variants of the lipoprotein lipase (LPL) gene and indicators of body fat, fat distribution and plasma lipids and insulin were studied in the Québec Family Study cohort. Strong linkage disequilibrium among all the markers was observed. For the S447X polymorphism, plasma very low density lipoprotein (VLDL)-cholesterol (chol) (P<0.001), total triglyceride (TG) (P=0.033) and VLDL-TG (P<0.001) levels were lower and high density lipoprotein (HDL)-chol level higher (P<0.001) in the subjects homozygous or heterozygous for X447 (X447+, n=160) compared to the homozygotes for the S447 allele (X447-, n=576). The BamHI, PvuII and HindIII polymorphisms were not associated with the plasma lipid values when all X447 allele carriers were removed. In addition, the HindIII polymorphism as well as the HindIII and S447X markers combination influenced the insulin area under the curve during an oral glucose tolerance test. We conclude that DNA sequence variation in the LPL gene contributes significantly to the variability in the levels of VLDL-chol, total- and VLDL-TG as well as HDL-chol. The effects of the other polymorphisms considered here are most likely mediated by their linkage disequilibrium with the S447X mutation. In addition, genetic variation at the LPL locus may, by an unknown mechanism, influence insulin metabolism but not body fat variability.
    Atherosclerosis 10/2001; 158(1):199-206. · 3.79 Impact Factor
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    Article: The LPL gene in individuals with familial combined hyperlipidemia and decreased LPL activity.
    D N Nevin, J D Brunzell, S S Deeb
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    ABSTRACT: Familial combined hyperlipidemia (FCHL) is an oligogenic disorder, with family members having elevated apolipoprotein B-100 levels and either elevated plasma cholesterol or triglyceride levels or both. Obligate heterozygous parents of children with lipoprotein lipase (LPL) deficiency express a mild FCHL phenotype. Of patients with FCHL, 36% have diminished postheparin LPL activity and mass values that are comparable with those of obligate heterozygotes for LPL deficiency. It is hypothesized that heterozygosity for mutations in the LPL gene could contribute to FCHL in this subset of patients. Single-strand conformation polymorphism (SSCP) analysis, direct DNA sequencing, and Southern blot analysis were used to examine exons 1 through 9 and exon-intron junctions of the LPL gene in 20 patients with FCHL and low LPL activity and mass. One subject had a substitution (GAC-->AAC) in exon 2, changing Asp9 to Asn. Two subjects had a previously undescribed "silent" substitution (GTG-->GTA) in exon 3 at Val108. Three patients had a premature termination at codon 447 in exon 9 resulting in truncation of the mature protein by two amino acids. In addition to SSCP analysis, exons 4, 5, and 6, where almost all mutations in LPL-deficient patients have been found, were sequenced and no additional mutations were found. Southern blot analysis of the LPL gene revealed one subject with heterozygous loss of an EcoRI site but without an abnormality in Stu I restriction fragments; this mutation is therefore unlikely to be functionally significant. The substitutions identified at codons 9 and 447 have previously been found not to affect lipolytic activity when expressed in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
    Arteriosclerosis and thrombosis: a journal of vascular biology / American Heart Association 06/1994; 14(6):869-73.
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Keywords

520 normoglycemic non-Hispanic whites
 
chi 2 analysis
 
fasting insulin
 
fragment-length polymorphism genotype
 
genotype specific differences
 
high-density lipoprotein cholesterol
 
high-density lipoprotein-cholesterol levels
 
HindIII restriction site polymorphism
 
insulin resistance syndrome
 
insulin-resistance syndrome
 
insulin-resistance syndrome components
 
lipoprotein lipase
 
lipoprotein lipase genotypes
 
lipoprotein lipase locus
 
odds ratio
 
polymerase chain reaction
 
population sample
 
reduced high-density lipoprotein-cholesterol level
 
San Luis Valley
 
standard procedures
 

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