Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes: A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats

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Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes : A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats. / Tolbus, Andra; Mortensen, Martin B; Nielsen, Sune F; Kamstrup, Pia R; Bojesen, Stig E; Nordestgaard, Børge G.

In: Clinical Chemistry, Vol. 63, No. 12, 12.2017, p. 1866-1876.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Tolbus, A, Mortensen, MB, Nielsen, SF, Kamstrup, PR, Bojesen, SE & Nordestgaard, BG 2017, 'Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes: A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats', Clinical Chemistry, vol. 63, no. 12, pp. 1866-1876. https://doi.org/10.1373/clinchem.2017.277103

APA

Tolbus, A., Mortensen, M. B., Nielsen, S. F., Kamstrup, P. R., Bojesen, S. E., & Nordestgaard, B. G. (2017). Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes: A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats. Clinical Chemistry, 63(12), 1866-1876. https://doi.org/10.1373/clinchem.2017.277103

Vancouver

Tolbus A, Mortensen MB, Nielsen SF, Kamstrup PR, Bojesen SE, Nordestgaard BG. Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes: A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats. Clinical Chemistry. 2017 Dec;63(12):1866-1876. https://doi.org/10.1373/clinchem.2017.277103

Author

Tolbus, Andra ; Mortensen, Martin B ; Nielsen, Sune F ; Kamstrup, Pia R ; Bojesen, Stig E ; Nordestgaard, Børge G. / Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes : A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats. In: Clinical Chemistry. 2017 ; Vol. 63, No. 12. pp. 1866-1876.

Bibtex

@article{107c2cf4834945c4becf9724ff15b3fd,
title = "Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes: A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats",
abstract = "BACKGROUND: Low plasma lipoprotein(a) concentrations are associated with type 2 diabetes. Whether this is due to low lipoprotein(a) concentrations per se or to a large number of kringle IV type 2 (KIV-2) repeats remains unclear. We therefore aimed to identify genetic variants associated selectively with lipoprotein(a) concentrations or with the number of KIV-2 repeats, to investigate which of these traits confer risk of diabetes.METHODS: We genotyped 8411 individuals from the Copenhagen City Heart Study for 778 single-nucleotide polymorphisms (SNPs) in the proximity of the LPA gene, and examined the association of these SNPs with plasma concentrations of lipoprotein(a) and with KIV-2 number of repeats. SNPs that were selectively associated with lipoprotein(a) concentrations but not with KIV-2 number of repeats, or vice versa, were included in a Mendelian randomization study.RESULTS: We identified 3 SNPs (rs12209517, rs12194138, and rs641990) that were associated selectively with lipoprotein(a) concentrations and 3 SNPs (rs1084651, rs9458009, and rs9365166) that were associated selectively with KIV-2 number of repeats. For SNPs selectively associated with lipoprotein(a) concentrations, an allele score of 4-6 vs 0-2 had an odds ratio for type 2 diabetes of 1.03 (95{\%} CI, 0.86-1.23). In contrast, for SNPs selectively associated with KIV-2 number of repeats, an allele score of 4-6 vs 0-2 had an odds ratio for type 2 diabetes of 1.42 (95{\%} CI, 1.17-1.69).CONCLUSIONS: Using a novel genetic approach, our results indicate that it is a high number of KIV-2 repeats that are associated causally with increased risk of type 2 diabetes, and not low lipoprotein(a) concentrations per se. This is a reassuring finding for lipoprotein(a)-lowering therapies that do not increase the KIV-2 number of repeats.",
keywords = "Journal Article",
author = "Andra Tolbus and Mortensen, {Martin B} and Nielsen, {Sune F} and Kamstrup, {Pia R} and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G}",
note = "{\circledC} 2017 American Association for Clinical Chemistry.",
year = "2017",
month = "12",
doi = "10.1373/clinchem.2017.277103",
language = "English",
volume = "63",
pages = "1866--1876",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry, Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - Kringle IV Type 2, Not Low Lipoprotein(a), as a Cause of Diabetes

T2 - A Novel Genetic Approach Using SNPs Associated Selectively with Lipoprotein(a) Concentrations or with Kringle IV Type 2 Repeats

AU - Tolbus, Andra

AU - Mortensen, Martin B

AU - Nielsen, Sune F

AU - Kamstrup, Pia R

AU - Bojesen, Stig E

AU - Nordestgaard, Børge G

N1 - © 2017 American Association for Clinical Chemistry.

PY - 2017/12

Y1 - 2017/12

N2 - BACKGROUND: Low plasma lipoprotein(a) concentrations are associated with type 2 diabetes. Whether this is due to low lipoprotein(a) concentrations per se or to a large number of kringle IV type 2 (KIV-2) repeats remains unclear. We therefore aimed to identify genetic variants associated selectively with lipoprotein(a) concentrations or with the number of KIV-2 repeats, to investigate which of these traits confer risk of diabetes.METHODS: We genotyped 8411 individuals from the Copenhagen City Heart Study for 778 single-nucleotide polymorphisms (SNPs) in the proximity of the LPA gene, and examined the association of these SNPs with plasma concentrations of lipoprotein(a) and with KIV-2 number of repeats. SNPs that were selectively associated with lipoprotein(a) concentrations but not with KIV-2 number of repeats, or vice versa, were included in a Mendelian randomization study.RESULTS: We identified 3 SNPs (rs12209517, rs12194138, and rs641990) that were associated selectively with lipoprotein(a) concentrations and 3 SNPs (rs1084651, rs9458009, and rs9365166) that were associated selectively with KIV-2 number of repeats. For SNPs selectively associated with lipoprotein(a) concentrations, an allele score of 4-6 vs 0-2 had an odds ratio for type 2 diabetes of 1.03 (95% CI, 0.86-1.23). In contrast, for SNPs selectively associated with KIV-2 number of repeats, an allele score of 4-6 vs 0-2 had an odds ratio for type 2 diabetes of 1.42 (95% CI, 1.17-1.69).CONCLUSIONS: Using a novel genetic approach, our results indicate that it is a high number of KIV-2 repeats that are associated causally with increased risk of type 2 diabetes, and not low lipoprotein(a) concentrations per se. This is a reassuring finding for lipoprotein(a)-lowering therapies that do not increase the KIV-2 number of repeats.

AB - BACKGROUND: Low plasma lipoprotein(a) concentrations are associated with type 2 diabetes. Whether this is due to low lipoprotein(a) concentrations per se or to a large number of kringle IV type 2 (KIV-2) repeats remains unclear. We therefore aimed to identify genetic variants associated selectively with lipoprotein(a) concentrations or with the number of KIV-2 repeats, to investigate which of these traits confer risk of diabetes.METHODS: We genotyped 8411 individuals from the Copenhagen City Heart Study for 778 single-nucleotide polymorphisms (SNPs) in the proximity of the LPA gene, and examined the association of these SNPs with plasma concentrations of lipoprotein(a) and with KIV-2 number of repeats. SNPs that were selectively associated with lipoprotein(a) concentrations but not with KIV-2 number of repeats, or vice versa, were included in a Mendelian randomization study.RESULTS: We identified 3 SNPs (rs12209517, rs12194138, and rs641990) that were associated selectively with lipoprotein(a) concentrations and 3 SNPs (rs1084651, rs9458009, and rs9365166) that were associated selectively with KIV-2 number of repeats. For SNPs selectively associated with lipoprotein(a) concentrations, an allele score of 4-6 vs 0-2 had an odds ratio for type 2 diabetes of 1.03 (95% CI, 0.86-1.23). In contrast, for SNPs selectively associated with KIV-2 number of repeats, an allele score of 4-6 vs 0-2 had an odds ratio for type 2 diabetes of 1.42 (95% CI, 1.17-1.69).CONCLUSIONS: Using a novel genetic approach, our results indicate that it is a high number of KIV-2 repeats that are associated causally with increased risk of type 2 diabetes, and not low lipoprotein(a) concentrations per se. This is a reassuring finding for lipoprotein(a)-lowering therapies that do not increase the KIV-2 number of repeats.

KW - Journal Article

U2 - 10.1373/clinchem.2017.277103

DO - 10.1373/clinchem.2017.277103

M3 - Journal article

C2 - 28971985

VL - 63

SP - 1866

EP - 1876

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

IS - 12

ER -

ID: 185988574