Association between lipoprotein lipase (LPL) gene and blood lipids: A common variant for a common trait?

Morabia, Alfredo; Cayanis, Eftìhia; Costanza, Michael C.; Ross, Barbara; Bernstein, Martine; Flaherty, Maria Sol; Alvin, Gabriela B.; Das, Kamna; Morris, Michael A.; Penchaszadeh, Graciela K.; Zhang, Peizen; Gilliam, T. Conrad

doi:10.1002/gepi.10229

Cited by 23 publications

(19 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The frequency we observed for the minor allele of 7754C>A (0.11) was similar to that reported by Morabia et al (8) (0.12). A significant association of the C allele with EH was observed ( Table 2), but was only confined to females ( p 0.027 for alleles, p 0.0315 for genotypes).…”

Section: C a Variantsupporting

confidence: 91%

“…On the other hand, Hunt and colleagues failed to replicate these positive findings in Caucasians (6). Because the genomic sequence of the LPL gene is highly polymorphic and a number of variants have been screened (7,8), associations of markers near the LPL gene locus and polymorphisms within this locus with hypertension have been tested in different populations. Ma and colleagues found that the D8S282 marker near the LPL gene locus contributed to the variance of SBP in healthy Chinese subjects from Hong Kong, especially in females (9).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lipoprotein Lipase Gene Polymorphisms and Blood Pressure Levels in the Northern Chinese Han Population

Wang

et al. 2004

Hypertens Res

View full text Add to dashboard Cite

Section: C a Variantsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Lipoprotein Lipase Gene Polymorphisms and Blood Pressure Levels in the Northern Chinese Han Population

Wang

et al. 2004

Hypertens Res

View full text Add to dashboard Cite

“…Compared to the wild type, the LPL activity associated with the X447 mutation was higher in one, lower in another, but comparable in three studies [reviewed in 22]. In association studies, although the X447 allele has been reported to be associated with a favorable lipid profile in some studies [7][8]22] the results have not been confirmed in other studies [15]. Similarly, the association of the S447X polymorphism with CAD is inconsistent [10][11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 98%

“…Several common LPL genetic variants have been widely studied, and among them HindIII in intron 8 (T→G at position 481), and S447X in exon 9 are of particular interest because of their common occurrence (25% and 9% of the less common alleles, respectively in most populations) and their associations with plasma lipid profile [6][7][8][9][10][11] and susceptibility to CAD [10][11][12][13][14][15] in several studies, although some inconsistent results have also been reported [16][17][18]. Since the HindIII polymorphism is located in the middle of intron 8, it is not considered to be functional but rather in linkage disequilibrium with a putative functional variant.…”

Section: Introductionmentioning

confidence: 99%

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

et al. 2008

View full text Add to dashboard Cite

Lipoprotein Lipase (LPL) plays a pivotal role in lipid metabolism by hydrolyzing triglyceride (TG) rich lipoprotein particles. Abnormalities in normal LPL function are associated with the risk of coronary artery disease (CAD). A number of genetic variants have been identified in the LPL gene that affects different functions of the LPL protein. A common HindIII polymorphism in intron 8 (T/ G) of the LPL gene has been found to be associated with altered plasma TG and HDL-cholesterol, and CAD risk in several studies, but its functional significance is unknown. It has been shown that certain intronic sequence contain regulatory elements that are important for transcription and translational regulation of a gene. In this study we tested the hypothesis that this polymorphism affects the binding site of a transcription factor that regulates the transcription of LPL gene. Electrophoretic mobility shift assays revealed that the HindIII site binds to a transcription factor and that the mutant allele has lower binding affinity than the wild type allele. Transcription assays containing the entire intron 8 sequence along with full-length human LPL promoter were carried out in COS-1 and human vascular smooth muscle cells. The mutant allele was associated with significantly decreased luciferase expression level compared to the wild type allele in both the muscle (3.394 ± 0.022 vs. 4.184 ± 0.028; P=4.7 × 10 −6 ) and COS-1 (11.603 ± 0.409 vs. 14.373 ± 1.096; P<0.0001) cells. In conclusion, this study demonstrates for the first time that the polymorphic HindIII site in the LPL gene is functional because it affects the binding of a transcription factor and it also has an impact on LPL expression.

show abstract

“…1998;Templeton et al 2000a,b;Morabia et al Step 3. Divide SNPs into LD groups: if two SNPs have r 2 Ն s, they belong to the same LD group.…”

mentioning

confidence: 99%

Linkage Disequilibrium Grouping of Single Nucleotide Polymorphisms (SNPs) Reflecting Haplotype Phylogeny for Efficient Selection of Tag SNPs

et al. 2005

View full text Add to dashboard Cite

Single nucleotide polymorphisms (SNPs) have been proposed to be grouped into haplotype blocks harboring a limited number of haplotypes. Within each block, the portion of haplotypes is expected to be tagged by a selected subset of SNPs; however, none of the proposed selection algorithms have been definitive. To address this issue, we developed a tag SNP selection algorithm based on grouping of SNPs by the linkage disequilibrium (LD) coefficient r 2 and examined five genes in three ethnic populations-the Japanese, African Americans, and Caucasians. Additionally, we investigated ethnic diversity by characterizing 979 SNPs distributed throughout the genome. Our algorithm could spare 60% of SNPs required for genotyping and limit the imprecision in allele-frequency estimation of nontag SNPs to 2% on average. We discovered the presence of a mosaic pattern of LD plots within a conventionally inferred haplotype block. This emerged because multiple groups of SNPs with strong intragroup LD were mingled in their physical positions. The pattern of LD plots showed some similarity, but the details of tag SNPs were not entirely concordant among three populations. Consequently, our algorithm utilizing LD grouping allows selection of a more faithful set of tag SNPs than do previous algorithms utilizing haplotype blocks.

show abstract

Association between lipoprotein lipase (LPL) gene and blood lipids: A common variant for a common trait?

Cited by 23 publications

References 28 publications

Lipoprotein Lipase Gene Polymorphisms and Blood Pressure Levels in the Northern Chinese Han Population

Lipoprotein Lipase Gene Polymorphisms and Blood Pressure Levels in the Northern Chinese Han Population

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

Linkage Disequilibrium Grouping of Single Nucleotide Polymorphisms (SNPs) Reflecting Haplotype Phylogeny for Efficient Selection of Tag SNPs

Contact Info

Product

Resources

About