Shuen Andrew Y, Wong Betty Y L, Wei Cuihong, Liu Zhanqin, Li Mei, Cole David E C
Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Clin Chim Acta. 2009 Nov;409(1-2):28-32. doi: 10.1016/j.cca.2009.08.007. Epub 2009 Aug 18.
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.
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.
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.
The significant association between magnesium and ESR1 polymorphisms supports previous studies linking physiologic changes in serum magnesium to estrogen status.
血清镁浓度是一种具有高度遗传性的数量性状。尽管候选基因库不断扩大，但只有组织相容性位点与镁水平相关。为探索其他可能性，我们选取了6个与镁代谢生理相关的候选基因。
我们研究了一个大型队列（n = 471），该队列来自特征明确的18至35岁健康白种女性人群。采用原子吸收分光光度法（aaMg和aaCa）测量血清总镁和钙。扩增基因组DNA，并通过常规方法对候选基因（CASR、VDR、ESR1、CLDN16、EGF1、TRPM6）中的单核苷酸多态性（SNP）进行基因分型。
我们发现雌激素受体α（ESR1）多态性PvuII和XbaI与镁之间存在显著关联（r分别为 -0.116，p = 0.012和r = -0.126，p = 0.006））。按PvuII基因型（P/p等位基因）分层，pp组（0.823±0.005 mmol/l，n = 130）的平均校正总镁（aaMg）浓度显著高于PP纯合子组（0.805±0.006 mmol/l，n = 70）（p = 0.01），Pp杂合子组的平均值介于两者之间（0.810±0.005 mmol/l，n = 180）。在所检测的其他候选基因中未观察到显著关联。
镁与ESR1多态性之间的显著关联支持了先前将血清镁的生理变化与雌激素状态联系起来的研究。
