Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight

Karina Meidtner; Eva Fisher; Lars Angquist; Claus Holst; Karani S Vimaleswaran; Jolanda M A Boer; Jytte Halkjær; Giovanna Masala; Jane N Ostergaard; Lotte M Mortensen; Daphne L van der A; Anne Tjønneland; Domenico Palli; Kim Overvad; Nicholas J Wareham; Ruth J F Loos; Thorkild I A Sørensen; Heiner Boeing

doi:10.1007/s12263-014-0385-7

Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight

Karina Meidtner, Eva Fisher, Lars Angquist, Claus Holst, Karani S Vimaleswaran, Jolanda M A Boer, Jytte Halkjær, Giovanna Masala, Jane N Ostergaard, Lotte M Mortensen, Daphne L van der A, Anne Tjønneland, Domenico Palli, Kim Overvad, Nicholas J Wareham, Ruth J F Loos, Thorkild I A Sørensen, Heiner Boeing

Department of Public Health

1 Citation (Scopus)

Abstract

We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (-25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene-nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies.

Original language	English
Journal	Genes & Nutrition
Volume	9
Pages (from-to)	1-11
Number of pages	11
ISSN	1555-8932
DOIs	https://doi.org/10.1007/s12263-014-0385-7
Publication status	Published - Mar 2014

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Meidtner, K., Fisher, E., Angquist, L., Holst, C., Vimaleswaran, K. S., Boer, J. M. A., Halkjær, J., Masala, G., Ostergaard, J. N., Mortensen, L. M., van der A, D. L., Tjønneland, A., Palli, D., Overvad, K., Wareham, N. J., Loos, R. J. F., Sørensen, T. I. A., & Boeing, H. (2014). Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight. Genes & Nutrition, 9, 1-11. https://doi.org/10.1007/s12263-014-0385-7

Meidtner, K, Fisher, E, Angquist, L, Holst, C, Vimaleswaran, KS, Boer, JMA, Halkjær, J, Masala, G, Ostergaard, JN, Mortensen, LM, van der A, DL, Tjønneland, A, Palli, D, Overvad, K, Wareham, NJ, Loos, RJF, Sørensen, TIA & Boeing, H 2014, 'Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight', Genes & Nutrition, vol. 9, pp. 1-11. https://doi.org/10.1007/s12263-014-0385-7

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title = "Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight",

abstract = "We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (-25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene-nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies.",

author = "Karina Meidtner and Eva Fisher and Lars Angquist and Claus Holst and Vimaleswaran, {Karani S} and Boer, {Jolanda M A} and Jytte Halkj{\ae}r and Giovanna Masala and Ostergaard, {Jane N} and Mortensen, {Lotte M} and {van der A}, {Daphne L} and Anne Tj{\o}nneland and Domenico Palli and Kim Overvad and Wareham, {Nicholas J} and Loos, {Ruth J F} and S{\o}rensen, {Thorkild I A} and Heiner Boeing",

year = "2014",

month = mar,

doi = "10.1007/s12263-014-0385-7",

language = "English",

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T1 - Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight

AU - Meidtner, Karina

AU - Fisher, Eva

AU - Angquist, Lars

AU - Holst, Claus

AU - Vimaleswaran, Karani S

AU - Boer, Jolanda M A

AU - Halkjær, Jytte

AU - Masala, Giovanna

AU - Ostergaard, Jane N

AU - Mortensen, Lotte M

AU - van der A, Daphne L

AU - Tjønneland, Anne

AU - Palli, Domenico

AU - Overvad, Kim

AU - Wareham, Nicholas J

AU - Loos, Ruth J F

AU - Sørensen, Thorkild I A

AU - Boeing, Heiner

PY - 2014/3

Y1 - 2014/3

N2 - We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (-25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene-nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies.

AB - We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (-25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene-nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies.

U2 - 10.1007/s12263-014-0385-7

DO - 10.1007/s12263-014-0385-7

M3 - Journal article

C2 - 24496996

SN - 1555-8932

VL - 9

SP - 1

EP - 11

JO - Genes & Nutrition

JF - Genes & Nutrition

ER -

Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight

Abstract

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