Linkage and linkage disequilibrium analysis of the lipoprotein lipase gene with lipid profiles in Chinese hypertensive families

Elevated TG [triacylglycerol (triglyceride)] is a significant independent risk factor for cardiovascular disease. LPL (lipoprotein lipase) is one of the key enzymes in the metabolism of the TG-rich lipoproteins which hydrolyses TG from the chylomicrons and very-LDL (low-density lipoprotein). To investigate the relationship between the LPL gene and lipid profiles, especially TG, in 148 hypertensive families, we have chosen seven flanking microsatellite markers and four internal markers of the LPL gene and conducted linkage analysis by SOLAR and S.A.G.E. (statistical analysis for genetic epidemiology)/SIBPAL 2 programs, and linkage disequilibrium analysis by QTDT (quantitative transmission/disequilibrium test) and GOLD (graphical overview of linkage disequilibrium). There were statistically significant differences in lipid levels between subjects without and with hypertension within families. A maximum LOD score of 1.3 with TG at the marker D8S261 was observed by SOLAR. Using S.A.G.E./SIBPAL 2, we identified a linkage with TG at the marker ‘ATTT’ located within intron 6 of the LPL gene (P=0.0095). Two SNPs (single nucleotide polymorphisms), HindIII and HinfI, were found in linkage disequilibrium with LDL-cholesterol levels (P=0.0178 and P=0.0088 respectively). A strong linkage disequilibrium was observed between the HindIII in intron 8 and HinfI in the exon 9 (P<0.00001, D′=0.895). Linkage disequilibrium was also found between the ‘ATTT’ polymorphism in intron 6 and two SNPs (P=0.0021 and D′=0.611 for HindIII; and P=0.00004, D′=0.459 for HinfI). The present study in the Chinese families with hypertension suggested that the LPL gene might influence lipid levels, especially TG metabolism. Replication studies both in Chinese and other populations are warranted to confirm these results.

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Association of multiple nucleotide variations in the pituitary glutaminyl cyclase gene QPC with low radial BMD in adult women.

10.31234/osf.io/93fcq ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Linkage Disequilibrium ◽

Multiple Regression ◽

Genetic Variations ◽

Strong Linkage Disequilibrium ◽

Adult Women ◽

Nucleotide Polymorphisms ◽

Haplotype Estimation ◽

Factors Affecting ◽

Glutaminyl Cyclase ◽

Strong Linkage

Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene andadjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium,R54W showed a prominent association (p ? 0.0003), which was more striking when examined among 309 eldersubjects (>50 years; p ? 0.0001). Contribution for postmenopausal bone loss was suggested.Introduction: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis(HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have beenproposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene(GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essentialmodifier of pituitary peptide hormones, including GnRH.Materials and Methods: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locuswith adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) wasanalyzed by haplotype estimation and calculation of D? and r2. Multiple regression analysis was applied forevaluating the combined effects of the variations.Results and Conclusions: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of theQPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD,among which R54W (nt ? 160C?T) presented the most prominent association (p ? 0.0003). Striking associationwas observed for these SNPs among the 309 subjects ?50 years of age (R54W, p ? 0.0001; ?1095T?C, p ?0.0002; ?1844C?T, p ? 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might actin combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are theimportant factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The datashould provide new insight into the etiology of the disease and may suggest a new target to be considered duringtreatment.J Bone Miner

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Associations of Lipoprotein Lipase Gene rs326 with Changes of Lipid Profiles after a High-Carbohydrate and Low-Fat Diet in Healthy Chinese Han Youth

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph110404544 ◽

2014 ◽

Vol 11 (4) ◽

pp. 4544-4554 ◽

Cited By ~ 2

Author(s):

Xing-chun Zhu ◽

Jia Lin ◽

Qian Wang ◽

Hui Liu ◽

Li Qiu ◽

...

Keyword(s):

Lipoprotein Lipase ◽

Lipid Profiles ◽

Low Fat ◽

Lipase Gene ◽

Chinese Han ◽

High Carbohydrate ◽

Lipoprotein Lipase Gene ◽

Low Fat Diet ◽

Healthy Chinese

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Identification of novel single nucleotide polymorphisms (SNPs) of the lipoprotein lipase (LPL) gene associated with fatty acid composition in Korean cattle

Molecular Biology Reports ◽

10.1007/s11033-012-2389-y ◽

2012 ◽

Vol 40 (4) ◽

pp. 3155-3163 ◽

Cited By ~ 12

Author(s):

Dongyep Oh ◽

Boomi La ◽

Yoonseok Lee ◽

Younhwa Byun ◽

Jeayoung Lee ◽

...

Keyword(s):

Fatty Acid Composition ◽

Fatty Acid ◽

Single Nucleotide Polymorphisms ◽

Lipoprotein Lipase ◽

Acid Composition ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Korean Cattle ◽

Lpl Gene

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Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease

Biomedical Reports ◽

10.3892/br.2013.126 ◽

2013 ◽

Vol 1 (4) ◽

pp. 573-582 ◽

Cited By ~ 11

Author(s):

MOHAMED S. DAOUD ◽

FARID S. ATAYA ◽

DALIA FOUAD ◽

AMAL ALHAZZANI ◽

AFAF I. SHEHATA ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Lipoprotein Lipase ◽

Gene Polymorphisms ◽

Lipid Profiles ◽

Lipase Gene ◽

Lipoprotein Lipase Gene ◽

Artery Disease

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Fatty acids regulate the expression of lipoprotein lipase gene and activity in preadipose and adipose cells

Biochemical Journal ◽

10.1042/bj3140541 ◽

1996 ◽

Vol 314 (2) ◽

pp. 541-546 ◽

Cited By ~ 50

Author(s):

Ez-Zoubir AMRI ◽

Lydia TEBOUL ◽

Christian VANNIER ◽

Paul-André GRIMALDI ◽

Gérard AILHAUD

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Lipoprotein Lipase ◽

Fine Tuning ◽

Lipase Gene ◽

Lpl Gene ◽

Dose Dependent Increase ◽

Dose Dependent ◽

Adipose Cells

During fasting, a reduction in lipoprotein lipase (LPL) activity has been observed in rat fat pad with no change in enzyme mass, whereas LPL mRNA and synthesis are increased, suggesting that insulin and/or fatty acids (FA) regulate LPL activity post-translationaly [Doolittle, Ben-Zeev, Elovson, Martin and Kirchgessner (1990) J. Biol. Chem. 265, 4570–4577]. To examine the role of FA, either preadipose Ob1771 cells or Ob1771 and 3T3-F442A adipose cells were exposed to long-chain FA and to 2-bromopalmitate, a non-metabolized FA. A rapid (2–8 h) and dose-dependent increase (up to 6-fold) in LPL mRNA occurred, primarily due to increased transcription, which is accompanied by a decrease (down to 4-fold) in LPL cellular activity. Under these conditions, secretion of active LPL was nearly abolished. Removal of FA led to full recovery of LPL activity. LPL gene expression in 3T3-C2 fibroblasts was not affected by FA treatment. However fatty acid-activated receptor transfected-3T3-C2 cells, which show FA responsiveness, had increased LPL gene expression upon FA addition. LPL synthesis and cellular content appeared unaffected by FA treatment, whereas secretion of LPL was inhibited. These results indicate that FA regulate the post-translational processing of LPL. It is proposed that the regulation of LPL activity by FA is important with regard to the fine-tuning of FA entry into adipocytes during fasting/feeding periods.

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Cladistic Structure Within the Human Lipoprotein Lipase Gene and Its Implications for Phenotypic Association Studies

Genetics ◽

10.1093/genetics/156.3.1259 ◽

2000 ◽

Vol 156 (3) ◽

pp. 1259-1275 ◽

Cited By ~ 1

Author(s):

Alan R Templeton ◽

Kenneth M Weiss ◽

Deborah A Nickerson ◽

Eric Boerwinkle ◽

Charles F Sing

Keyword(s):

Lipoprotein Lipase ◽

Association Studies ◽

Haplotype Diversity ◽

Human Populations ◽

Nucleotide Polymorphisms ◽

Lipase Gene ◽

Multiple Events ◽

General Utility ◽

Haplotype Variation ◽

Recurrent Mutations

Abstract Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3′ region should have general utility in most human populations, but the 5′ SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region.

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