title: Genetic determinants of extracellular magnesium concentration: analysis of multiple candidate genes, and evidence for association with the estrogen receptor alpha (ESR1) locus.
abstract: BACKGROUND
  Serum magnesium concentration is a quantitative trait with substantial heritability. Although the pool of candidate genes continues to grow, only the histocompatibility locus has been associated with magnesium levels. To explore other possibilities, we targeted 6 candidate genes physiologically relevant to magnesium metabolism.
  
  
  METHODS
  We studied a large cohort (n=471) derived from a well-characterized population of healthy Caucasian women 18 to 35 years. Total serum magnesium and calcium were measured by atomic absorption spectrophotometry (aaMg & aaCa). Genomic DNA was amplified and SNPs in candidate genes (CASR, VDR, ESR1, CLDN16, EGF1, TRPM6) genotyped by routine methods.
  
  
  RESULTS
  We found a significant association between estrogen receptor alpha (ESR1) polymorphisms, PvuII and XbaI, and magnesium (r=-0.116, p=0.012 and r=-0.126, p=0.006, respectively). Stratifying by PvuII genotype (P/p alleles), the mean adjusted total magnesium (aaMg) concentration was significantly higher (p=0.01) in the pp group (0.823+/-0.005 mmol/l, n=130) than in PP homozygotes (0.805+/-0.006 mmol/l, n=70), and the mean in Pp heterozygotes was intermediate (0.810+/-0.005 mmol/l, n=180). No significant associations were observed with the other candidate genes tested.
  
  
  CONCLUSIONS
  The significant association between magnesium and ESR1 polymorphisms supports previous studies linking physiologic changes in serum magnesium to estrogen status.
authors.affiliation: Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Shuen
authors.forename: Betty Y L
authors.initials: BY
authors.lastname: Wong
authors.forename: Cuihong
authors.initials: C
authors.lastname: Wei
authors.forename: Zhanqin
authors.initials: Z
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: David E C
authors.initials: DE
authors.lastname: Cole
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D008274:Magnesium / Q000097:blood / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D013054:Spectrophotometry, Atomic; D055815:Young Adult
chemical_list: D047628:Estrogen Receptor alpha; D008274:Magnesium