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Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies

Hruby, Adela; Ngwa, Julius S.; Renström, Frida LU ; Wojczynski, Mary K.; Ganna, Andrea; Hallmans, Goran; Houston, Denise K.; Jacques, Paul F.; Kanoni, Stavroula and Lehtimaki, Terho, et al. (2013) In Journal of Nutrition 143(3). p.345-353
Abstract
Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with... (More)
Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (In-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [beta = -0.009 mmol/L (95% CI: -0.013, -0.005), P< 0.0001] and insulin (-0.020 In-pmo/L (95% CI: -0.024, -0.017), P< 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P= 0.03) with glucose, and rs11558471 in SLC30A8and rs3740393 near CNNM2showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. J. Nutr. 143: 345-353, 2013. (Less)
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Journal of Nutrition
volume
143
issue
3
pages
345 - 353
publisher
American Society for Nutrition
external identifiers
  • wos:000315173500014
  • scopus:84874705274
ISSN
1541-6100
DOI
10.3945/jn.112.172049
language
English
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yes
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60557ad5-7923-447d-b86a-8b851fb62f88 (old id 3671535)
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2013-05-02 08:59:52
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2019-02-20 01:37:51
@article{60557ad5-7923-447d-b86a-8b851fb62f88,
  abstract     = {Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (In-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [beta = -0.009 mmol/L (95% CI: -0.013, -0.005), P&lt; 0.0001] and insulin (-0.020 In-pmo/L (95% CI: -0.024, -0.017), P&lt; 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P= 0.03) with glucose, and rs11558471 in SLC30A8and rs3740393 near CNNM2showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. J. Nutr. 143: 345-353, 2013.},
  author       = {Hruby, Adela and Ngwa, Julius S. and Renström, Frida and Wojczynski, Mary K. and Ganna, Andrea and Hallmans, Goran and Houston, Denise K. and Jacques, Paul F. and Kanoni, Stavroula and Lehtimaki, Terho and Lemaitre, Rozenn N. and Manichaikul, Ani and North, Kari E. and Ntalla, Ioanna and Sonestedt, Emily and Tanaka, Toshiko and van Rooij, Frank J. A. and Bandinelli, Stefania and Djousse, Luc and Grigoriou, Efi. and Johansson, Ingegerd and Lohman, Kurt K. and Pankow, James S. and Raitakari, Olli T. and Riserus, Ulf and Yannakoulia, Mary and Zillikens, M. Carola and Hassanali, Neelam and Liu, Yongmei and Mozaffarian, Dariush and Papoutsakis, Constantina and Syvanen, Ann-Christine and Uitterlinden, Andre G. and Viikari, Jorma and Groves, Christopher J. and Hofman, Albert and Lind, Lars and McCarthy, Mark I. and Mikkila, Vera and Mukamal, Kenneth and Franco, Oscar H. and Borecki, Ingrid B. and Cupples, L. Adrienne and Dedoussis, George V. and Ferrucci, Luigi and Hu, Frank B. and Ingelsson, Erik and Kahonen, Mika and Kao, W. H. Linda and Kritchevsky, Stephen B. and Orho-Melander, Marju and Prokopenko, Inga and Rotter, Jerome I. and Siscovick, David S. and Witteman, Jacqueline C. M. and Franks, Paul and Meigs, James B. and McKeown, Nicola M. and Nettleton, Jennifer A.},
  issn         = {1541-6100},
  language     = {eng},
  number       = {3},
  pages        = {345--353},
  publisher    = {American Society for Nutrition},
  series       = {Journal of Nutrition},
  title        = {Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies},
  url          = {http://dx.doi.org/10.3945/jn.112.172049},
  volume       = {143},
  year         = {2013},
}