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2015 ; 16
(ä): 56
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Genetic loci for serum magnesium among African-Americans and gene-environment
interaction at MUC1 and TRPM6 in European-Americans: the Atherosclerosis Risk in
Communities (ARIC) study
#MMPMID26058915
Tin A
; Köttgen A
; Folsom AR
; Maruthur NM
; Tajuddin SM
; Nalls MA
; Evans MK
; Zonderman AB
; Friedrich CA
; Boerwinkle E
; Coresh J
; Kao WH
BMC Genet
2015[May]; 16
(ä): 56
PMID26058915
show ga
BACKGROUND: Low serum magnesium levels have been associated with multiple chronic
diseases. The regulation of serum magnesium homeostasis is not well understood. A
previous genome-wide association study (GWAS) of European ancestry (EA)
populations identified nine loci for serum magnesium. No such study has been
conducted in African-Americans, nor has there been an evaluation of the
interaction of magnesium-associated SNPs with environmental factors. The goals of
this study were to identify genetic loci associated with serum magnesium in an
African-American (AA) population using both genome-wide and candidate region
interrogation approaches and to evaluate gene-environment interaction for the
magnesium-associated variants in both EA and AA populations. We conducted a GWAS
of serum magnesium in 2737 AA participants of the Atherosclerosis Risk in
Communities (ARIC) Study and interrogated the regions of the nine published
candidate loci in these results. Literature search identified the influence of
progesterone on MUC1 expression and insulin on TRPM6 expression. RESULTS: The
GWAS approach in African-American participants identified a locus near MUC1 as
genome-wide significant (rs2974937, beta=-0.013, p=6.1x10(-9)). The candidate
region interrogation approach identified two of the nine loci previously
discovered in EA populations as containing SNPs that were significantly
associated in African-American participants (SHROOM3 and TRPM6). The index
variants at these three loci together explained 2.8 % of the variance in serum
magnesium concentration in ARIC African-American participants. On the test of
gene-environment interaction in ARIC EA participants, the index variant at MUC1
had 2.5 times stronger association in postmenopausal women with progestin use
(beta=-0.028, p=7.3x10(-5)) than in those without any hormone use (beta=-0.011,
p=7.0x10(-8), p for interaction 0.03). At TRPM6, the index variant had 1.6 times
stronger association in those with lower fasting insulin levels (<80 pmol/L:
beta=-0.013, p=1.6x10(-7); ?80 pmol/L: beta=-0.008, p=1.8x10(-2), p for
interaction 0.03). CONCLUSIONS: We identified three loci that explained 2.8% of
the variance in serum magnesium concentration in ARIC African-American
participants. Following-up on functional studies of gene expression identified
gene-environment interactions between progestin use and MUC1 and between insulin
and TRPM6 on serum magnesium concentration in ARIC European-American
participants. These results extend our understanding of the metabolism of serum
magnesium.