LPIN2 is associated with type 2 diabetes, glucose metabolism, and body composition

Yurii S Aulchenko; Jan Pullen; Wigard P Kloosterman; Mojgan Yazdanpanah; Albert Hofman; Norbert Vaessen; Pieter J L M Snijders; Dmitry Zubakov; Ian Mackay; Mark Olavesen; Balbinder Sidhu; Vicki E Smith; Alisoun Carey; Eugene Berezikov; André G Uitterlinden; Ronald H A Plasterk; Ben A Oostra; Cornelia M van Duijn

doi:10.2337/db07-0338

LPIN2 is associated with type 2 diabetes, glucose metabolism, and body composition

Yurii S Aulchenko, Jan Pullen, Wigard P Kloosterman, Mojgan Yazdanpanah, Albert Hofman, Norbert Vaessen, Pieter J L M Snijders, Dmitry Zubakov, Ian Mackay, Mark Olavesen, Balbinder Sidhu, Vicki E Smith, Alisoun Carey, Eugene Berezikov, André G Uitterlinden, Ronald H A Plasterk, Ben A Oostra, Cornelia M van Duijn

Research output: Contribution to journal › Article › peer-review

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Abstract

OBJECTIVE: To identify the type 2 diabetes gene located at chromosome 18p11.

RESEARCH DESIGN AND METHODS: We investigated the region in a young genetically isolated population by genotyping 34 single nucleotide polymorphisms (SNPs) in 78 case subjects and 101 control subjects. Two SNPs were selected and followed up in two cohorts. The first cohort came from a general Dutch population. In this cohort, association with type 2 diabetes was investigated using 616 type 2 diabetic case subjects and 2,890 control subjects; association with oral glucose tolerance test data was performed in 361 normoglycemic people. Association with fat distribution was studied in the second replication cohort, consisting of 836 people from the genetically isolated population.

RESULTS: At the initial step, we found that the common C allele of SNP rs3745012 was associated with type 2 diabetes (odds ratio 2.01, P = 0.03). This SNP is located at the 3' untranslated region of the LPIN2 gene, which is a plausible candidate for type 2 diabetes and obesity. In the cohort from the general Dutch population, we demonstrated that rs3745012 interacts with BMI in determination of type 2 diabetes: whereas in subjects with high BMI, the common C allele is associated with type 2 diabetes, the same allele exhibits a neutral or protective effect in lean subjects (P = 0.05 overall effect, P = 0.02 interaction). Most remarkably, rs3745012 strongly affected composite insulin sensitivity index (P = 0.006 for overall effect, P = 0.004 for interaction). In the second replication cohort, we found that the allele C of rs3745012 increases trunk-to-legs fat mass ratio (P = 0.001) and may affect other fat-related measurements.

CONCLUSIONS: rs3745012 SNP of the LPIN2 gene is associated with type 2 diabetes and fat distribution.

Original language	English
Pages (from-to)	3020-6
Number of pages	7
Journal	Diabetes
Volume	56
Issue number	12
DOIs	https://doi.org/10.2337/db07-0338
Publication status	Published - Dec 2007
Externally published	Yes

Keywords

Adipose Tissue
Blood Glucose
Body Composition
Body Mass Index
Chromosome Mapping
Chromosomes, Human, Pair 18
Diabetes Mellitus, Type 2
Female
Genetic Predisposition to Disease
Genotype
Humans
Linkage Disequilibrium
Male
Nuclear Proteins
Polymorphism, Single Nucleotide
Reference Values

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/db07-0338

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Aulchenko, Y. S., Pullen, J., Kloosterman, W. P., Yazdanpanah, M., Hofman, A., Vaessen, N., Snijders, P. J. L. M., Zubakov, D., Mackay, I., Olavesen, M., Sidhu, B., Smith, V. E., Carey, A., Berezikov, E., Uitterlinden, A. G., Plasterk, R. H. A., Oostra, B. A., & van Duijn, C. M. (2007). LPIN2 is associated with type 2 diabetes, glucose metabolism, and body composition. Diabetes, 56(12), 3020-6. https://doi.org/10.2337/db07-0338

@article{01c594eefac3456fa87e514a829ba654,

title = "LPIN2 is associated with type 2 diabetes, glucose metabolism, and body composition",

abstract = "OBJECTIVE: To identify the type 2 diabetes gene located at chromosome 18p11.RESEARCH DESIGN AND METHODS: We investigated the region in a young genetically isolated population by genotyping 34 single nucleotide polymorphisms (SNPs) in 78 case subjects and 101 control subjects. Two SNPs were selected and followed up in two cohorts. The first cohort came from a general Dutch population. In this cohort, association with type 2 diabetes was investigated using 616 type 2 diabetic case subjects and 2,890 control subjects; association with oral glucose tolerance test data was performed in 361 normoglycemic people. Association with fat distribution was studied in the second replication cohort, consisting of 836 people from the genetically isolated population.RESULTS: At the initial step, we found that the common C allele of SNP rs3745012 was associated with type 2 diabetes (odds ratio 2.01, P = 0.03). This SNP is located at the 3' untranslated region of the LPIN2 gene, which is a plausible candidate for type 2 diabetes and obesity. In the cohort from the general Dutch population, we demonstrated that rs3745012 interacts with BMI in determination of type 2 diabetes: whereas in subjects with high BMI, the common C allele is associated with type 2 diabetes, the same allele exhibits a neutral or protective effect in lean subjects (P = 0.05 overall effect, P = 0.02 interaction). Most remarkably, rs3745012 strongly affected composite insulin sensitivity index (P = 0.006 for overall effect, P = 0.004 for interaction). In the second replication cohort, we found that the allele C of rs3745012 increases trunk-to-legs fat mass ratio (P = 0.001) and may affect other fat-related measurements.CONCLUSIONS: rs3745012 SNP of the LPIN2 gene is associated with type 2 diabetes and fat distribution.",

keywords = "Adipose Tissue, Blood Glucose, Body Composition, Body Mass Index, Chromosome Mapping, Chromosomes, Human, Pair 18, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Male, Nuclear Proteins, Polymorphism, Single Nucleotide, Reference Values",

author = "Aulchenko, {Yurii S} and Jan Pullen and Kloosterman, {Wigard P} and Mojgan Yazdanpanah and Albert Hofman and Norbert Vaessen and Snijders, {Pieter J L M} and Dmitry Zubakov and Ian Mackay and Mark Olavesen and Balbinder Sidhu and Smith, {Vicki E} and Alisoun Carey and Eugene Berezikov and Uitterlinden, {Andr{\'e} G} and Plasterk, {Ronald H A} and Oostra, {Ben A} and {van Duijn}, {Cornelia M}",

year = "2007",

month = dec,

doi = "10.2337/db07-0338",

language = "English",

volume = "56",

pages = "3020--6",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "12",

}

Aulchenko, YS, Pullen, J, Kloosterman, WP, Yazdanpanah, M, Hofman, A, Vaessen, N, Snijders, PJLM, Zubakov, D, Mackay, I, Olavesen, M, Sidhu, B, Smith, VE, Carey, A, Berezikov, E, Uitterlinden, AG, Plasterk, RHA, Oostra, BA & van Duijn, CM 2007, 'LPIN2 is associated with type 2 diabetes, glucose metabolism, and body composition', Diabetes, vol. 56, no. 12, pp. 3020-6. https://doi.org/10.2337/db07-0338

TY - JOUR

T1 - LPIN2 is associated with type 2 diabetes, glucose metabolism, and body composition

AU - Aulchenko, Yurii S

AU - Pullen, Jan

AU - Kloosterman, Wigard P

AU - Yazdanpanah, Mojgan

AU - Hofman, Albert

AU - Vaessen, Norbert

AU - Snijders, Pieter J L M

AU - Zubakov, Dmitry

AU - Mackay, Ian

AU - Olavesen, Mark

AU - Sidhu, Balbinder

AU - Smith, Vicki E

AU - Carey, Alisoun

AU - Berezikov, Eugene

AU - Uitterlinden, André G

AU - Plasterk, Ronald H A

AU - Oostra, Ben A

AU - van Duijn, Cornelia M

PY - 2007/12

Y1 - 2007/12

N2 - OBJECTIVE: To identify the type 2 diabetes gene located at chromosome 18p11.RESEARCH DESIGN AND METHODS: We investigated the region in a young genetically isolated population by genotyping 34 single nucleotide polymorphisms (SNPs) in 78 case subjects and 101 control subjects. Two SNPs were selected and followed up in two cohorts. The first cohort came from a general Dutch population. In this cohort, association with type 2 diabetes was investigated using 616 type 2 diabetic case subjects and 2,890 control subjects; association with oral glucose tolerance test data was performed in 361 normoglycemic people. Association with fat distribution was studied in the second replication cohort, consisting of 836 people from the genetically isolated population.RESULTS: At the initial step, we found that the common C allele of SNP rs3745012 was associated with type 2 diabetes (odds ratio 2.01, P = 0.03). This SNP is located at the 3' untranslated region of the LPIN2 gene, which is a plausible candidate for type 2 diabetes and obesity. In the cohort from the general Dutch population, we demonstrated that rs3745012 interacts with BMI in determination of type 2 diabetes: whereas in subjects with high BMI, the common C allele is associated with type 2 diabetes, the same allele exhibits a neutral or protective effect in lean subjects (P = 0.05 overall effect, P = 0.02 interaction). Most remarkably, rs3745012 strongly affected composite insulin sensitivity index (P = 0.006 for overall effect, P = 0.004 for interaction). In the second replication cohort, we found that the allele C of rs3745012 increases trunk-to-legs fat mass ratio (P = 0.001) and may affect other fat-related measurements.CONCLUSIONS: rs3745012 SNP of the LPIN2 gene is associated with type 2 diabetes and fat distribution.

AB - OBJECTIVE: To identify the type 2 diabetes gene located at chromosome 18p11.RESEARCH DESIGN AND METHODS: We investigated the region in a young genetically isolated population by genotyping 34 single nucleotide polymorphisms (SNPs) in 78 case subjects and 101 control subjects. Two SNPs were selected and followed up in two cohorts. The first cohort came from a general Dutch population. In this cohort, association with type 2 diabetes was investigated using 616 type 2 diabetic case subjects and 2,890 control subjects; association with oral glucose tolerance test data was performed in 361 normoglycemic people. Association with fat distribution was studied in the second replication cohort, consisting of 836 people from the genetically isolated population.RESULTS: At the initial step, we found that the common C allele of SNP rs3745012 was associated with type 2 diabetes (odds ratio 2.01, P = 0.03). This SNP is located at the 3' untranslated region of the LPIN2 gene, which is a plausible candidate for type 2 diabetes and obesity. In the cohort from the general Dutch population, we demonstrated that rs3745012 interacts with BMI in determination of type 2 diabetes: whereas in subjects with high BMI, the common C allele is associated with type 2 diabetes, the same allele exhibits a neutral or protective effect in lean subjects (P = 0.05 overall effect, P = 0.02 interaction). Most remarkably, rs3745012 strongly affected composite insulin sensitivity index (P = 0.006 for overall effect, P = 0.004 for interaction). In the second replication cohort, we found that the allele C of rs3745012 increases trunk-to-legs fat mass ratio (P = 0.001) and may affect other fat-related measurements.CONCLUSIONS: rs3745012 SNP of the LPIN2 gene is associated with type 2 diabetes and fat distribution.

KW - Adipose Tissue

KW - Blood Glucose

KW - Body Composition

KW - Body Mass Index

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 18

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Linkage Disequilibrium

KW - Male

KW - Nuclear Proteins

KW - Polymorphism, Single Nucleotide

KW - Reference Values

U2 - 10.2337/db07-0338

DO - 10.2337/db07-0338

M3 - Article

C2 - 17804763

SN - 0012-1797

VL - 56

SP - 3020

EP - 3026

JO - Diabetes

JF - Diabetes

IS - 12

ER -

LPIN2 is associated with type 2 diabetes, glucose metabolism, and body composition

Abstract

Keywords

UN SDGs

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