Structure and polymorphic map of human lipoprotein lipase gene

Oka, Koichiro; Tkalcevic, George T.; Nakano, Tamotsu; Tucker, H. Michael; Ishimura-Oka, Kazumi; Brown, W. Virgil

doi:10.1016/0167-4781(90)90079-h

Cited by 79 publications

(27 citation statements)

References 24 publications

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“…The combination oftwo procedures, such as the SIIA and sandwich EIA methods to quantitate LPL activity and mass in PHP, and immunochemical quantitations of LPL in the cultured macrophages, were powerful in estimating defects of the LPL molecule. These data together with LPL gene information (14,15,16,40) led us to finally identify the LPLAriJ allele. The sequence of LPL~,ia provided by this study should be useful to screen hyperlipidemic patients for the presence of LPLAJ,,J allele based on the primary information of LPL defect obtained by both the SIIA and sandwich EIA methods.…”

Section: Northern and Southern Blot Analysis Ofproband Tnmentioning

confidence: 99%

Molecular studies on primary lipoprotein lipase (LPL) deficiency. One base deletion (G916) in exon 5 of LPL gene causes no detectable LPL protein due to the absence of LPL mRNA transcript.

Takagi¹,

Ikeda²,

Tsutsumi³

et al. 1992

J. Clin. Invest.

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We have systematically investigated a genetic defect resulting in a primary lipoprotein lipase (LPL) deficiency in a proband TN and his affected brother SN, both manifesting familial hyperchylomicronemia. Neither LPL activity nor immunoreactive LPL mass was detected in postheparin plasma from the two patients. Immunocytochemical and biosynthetic studies on the proband's monocyte-derived macrophages with rabbit antihuman LPL antiserum revealed that no immunochemically detectable LPL protein was found in either the cells or culture medium, whereas LPL having a molecular mass of 61 kD was detected in normal cells. No detectable LPL mRNA was identified from poly(A)+RNA of the proband's macrophages by Northern blot analysis, and grossly visible LPL gene rearrangement was not observed by Southern blot analysis. Sequence analysis of polymerase chain reaction-amplified LPL gene exons detected one base deletion of G (first position of Ala221) at base 916 in exon 5 which leads to a premature termination by a frameshift. This mutation, designated as LPLAi and resulting in the loss of an Alul restriction enzyme site, was newly identified. We further analyzed the LPL gene from the two patients and their family members by digestion with AluL. Both patients were homozygous for LPLAJt allele, while their spouses did not have this mutation. As genetically expected, their children were all heterozygous for LPLmt.. We conclude that primary LPL deficiency in the proband was caused by a lack of enzyme synthesis due to the absence of LPL mRNA resulting from one base deletion ofG in exon 5, and that heterozygous LPLAi. deficient subjects show almost half value of control LPL mass. (J. Clin. Invest. 1992. 89:581-591.)

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Section: Northern and Southern Blot Analysis Ofproband Tnmentioning

confidence: 99%

Molecular studies on primary lipoprotein lipase (LPL) deficiency. One base deletion (G916) in exon 5 of LPL gene causes no detectable LPL protein due to the absence of LPL mRNA transcript.

Takagi¹,

Ikeda²,

Tsutsumi³

et al. 1992

J. Clin. Invest.

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“…11q: component of plasma lipoproteins T(‫)526מ‬del, C(‫)284מ‬T, T(‫)554מ‬C: increased plasma triglyceride levels HUMAPOCP (M60674), HSAPC3A (X01392); (Dammerman et al 1993) C3175G (Sst)I: increased plasma triglyceride levels HSAPC3A (X01392); (Rees et al 1985;Ordovas et al 1991) C1100T, T3206G: increased plasma triglyceride levels HSAPC3A (X01392); (Xu et al 1994 (Tall 1995;Lassel et al 1998) Ile-405-Val: increased plasma HDL cholesterol and apoA-I levels HUMCETP6 (M32997); Agellon et al 1990;Funke et al 1994;Gudnason et al 1997) Asp-442-Gly: increased HDL cholesterol levels, yet also disease risk HUMCETP7 (M32998); (Takahashi et al 1993;Zhong et al 1996) lipoprotein lipase (LPL) on chr. 8p: hydrolysis of plasma triglycerides T(‫)39מ‬G: increased LPL promoter activity, reduced plasma triglycerides HUMLPLA (M29549); (Yang et al 1995a,b;Ehrenborg et al 1997;Hall et al 1997) T(‫)93מ‬C: reduced LPL promoter activity HUMLPLA (M29549); (Yang et al 1995a,b) Asp9-Asn: increased plasma triglycerides, increased atherosclerotic progression HUMLPL (M15856); (Oka et al 1990;Mailly et al 1995;Jukema et al 1996) Asn-291-Ser: reduced plasma HDL cholesterol, increased triglyceride levels HUMLPL (M15856): (Oka et al 1990;Reymer et al 1995;Zhang et al 1995) Ser-447-Ter: increased plasma HDL cholesterol, reduced plasma triglyceride levels; possible impact on responsiveness to ␤-blockers HUMLPLF1 (M76722); (Hata et al 1990;Groenemeijer et al 1997;Kuivenhoven et al 1997) paraoxonase (PON) on chr. 7q: HDL-associated enzyme known to hydrolyze organophosphate poisons; possible contribution to HDL's protective capacity against LDL oxidation Gln-192-Arg: increased enzymatic activity; in vitro, reduced protection against lipid peroxidation HUMPONA (M63012); (Humbert et al 1993;Hegele et al 1995;Serrato and Marian 1995;Mackness et al 1997;Sanghera et al 1997) Renin-angiotensin system angiotensin-converting enzyme (ACE) on chr.…”

Section: Cvd35 Assaymentioning

confidence: 99%

A Multilocus Genotyping Assay for Candidate Markers of Cardiovascular Disease Risk

Cheng

Grow²,

Pallaud³

et al. 1999

Genome Res.

194

164

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A number of chronic diseases, including cardiovascular disease, appear to have a multifactorial genetic risk component. Consequently, techniques are needed to facilitate evaluation of complex genetic risk factors in large cohorts. We have designed a prototype assay for genotyping a panel of 35 biallelic sites that represent variation within 15 genes from biochemical pathways implicated in the development and progression of cardiovascular disease. Each DNA sample is amplified using two multiplex polymerase chain reactions, and the alleles are genotyped simultaneously using an array of immobilized, sequence-specific oligonucleotide probes. This multilocus assay was applied to two types of cohorts. Population frequencies for the markers were estimated using 496 unrelated individuals from a family-based cohort, and the observed values were consistent with previous reports. Linkage disequilibrium between consecutive pairs of markers within the apoCIII, LPL, and ELAM genes was also estimated. A preliminary analysis of single and pairwise locus associations with severity of atherosclerosis was performed using a composite cohort of 142 individuals for whom quantitative angiography data were available; evaluation of the potentially interesting associations observed will require analysis of an independent and larger cohort. This assay format provides a research tool for studies of multilocus genetic risk factors in large cardiovascular disease cohorts, and for the subsequent development of diagnostic tests.

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“…10 -12 The human LPL gene is localized to chromosome 8p22, spanning approximately 30 kb and containing 10 exons. 13 Several DNA variants of the LPL gene have been found and reported to underlie changes in plasma lipoprotein levels and to be important cardiovascular risk factors. For example, HindIII polymorphism of intron 8 of this gene is associated with elevated triglyceride levels, 14,15 low HDL cholesterol levels, 16,17 and premature coronary artery disease (CAD).…”

mentioning

confidence: 99%

Polymorphism of the Lipoprotein Lipase Gene and Risk of Atherothrombotic Cerebral Infarction in the Japanese

Shimo-Nakanishi

Urabe

Hattori

et al. 2001

Stroke

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Structure and polymorphic map of human lipoprotein lipase gene

Cited by 79 publications

References 24 publications

Molecular studies on primary lipoprotein lipase (LPL) deficiency. One base deletion (G916) in exon 5 of LPL gene causes no detectable LPL protein due to the absence of LPL mRNA transcript.

Molecular studies on primary lipoprotein lipase (LPL) deficiency. One base deletion (G916) in exon 5 of LPL gene causes no detectable LPL protein due to the absence of LPL mRNA transcript.

A Multilocus Genotyping Assay for Candidate Markers of Cardiovascular Disease Risk

Polymorphism of the Lipoprotein Lipase Gene and Risk of Atherothrombotic Cerebral Infarction in the Japanese

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