Genetic Variations in Magnesium-Related Ion Channels May Affect Diabetes Risk among African American and Hispanic American Women

被引:30
作者
Chan, Kei Hang K. [1 ]
Chacko, Sara A. [4 ,5 ]
Song, Yiqing [6 ]
Cho, Michele [7 ,8 ]
Eaton, Charles B. [1 ,2 ,9 ]
Wu, Wen-Chih H. [3 ,10 ]
Liu, Simin [1 ,3 ,7 ,8 ,11 ]
机构
[1] Brown Univ, Warren Alpert Med Sch, Dept Epidemiol, Providence, RI 02912 USA
[2] Brown Univ, Warren Alpert Med Sch, Dept Family Med, Providence, RI 02912 USA
[3] Brown Univ, Warren Alpert Med Sch, Dept Med, Providence, RI 02912 USA
[4] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA
[5] Harvard Univ, Sch Med, Boston, MA USA
[6] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA
[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA
[8] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA
[9] Brown Univ, Mem Hosp Rhode Isl, Ctr Primary Care & Prevent, Pawtucket, RI 02860 USA
[10] Providence US Dept Vet Affairs, Med Ctr, Vasc Res Lab, Providence, RI USA
[11] Rhode Isl Hosp, Div Endocrinol, Providence, RI USA
关键词
genes; ion channel; magnesium intake; diabetes; women; K-ATP CHANNEL; SUBUNITS KIR6.2 KCNJ11; POSTMENOPAUSAL WOMEN; ACTIVATING MUTATIONS; POTASSIUM CHANNELS; DIETARY MAGNESIUM; E23K POLYMORPHISM; SUR1; ABCC8; ASSOCIATION; VARIANTS;
D O I
10.3945/jn.114.203489
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Background: Prospective studies consistently link low magnesium intake to higher type 2 diabetes (T2D) risk. Objective: We examined the association of common genetic variants [single nucleotide polymorphisms (SNPs)] in genes related to magnesium homeostasis with T2D risk and potential interactions with magnesium intake. Methods: Using the Women's Health Initiative-SNP Health Association Resource (WHI-SHARe) study, we identified 17 magnesium-related ion channel genes (583 SNPs) and examined their associations with T2D risk in 7287 African-American (AA; n = 1949 T2D cases) and 3285 Hispanic-American (HA; n = 611 T2D cases) postmenopausal women. We performed both single-and multiple-locus haplotype analyses. Results: Among AA women, carriers of each additional copy of SNP rs6584273 in cyclin mediator 1 (CNNM1) had 16% lower T2D risk [OR: 0.84; false discovery rate (FDR)-adjusted P = 0.02]. Among HA women, several variants were significantly associated with T2D risk, including rs10861279 in solute carrier family 41 (anion exchanger), member 2 (SLC41A2) (OR: 0.54; FDR-adjusted P=0.04), rs7174119 in nonimprinted in Prader-Willi/Angelman syndrome 1 (NIPA1) (OR: 1.27; FDR-adjusted P = 0.04), and 2 SNPs in mitochondrial RNA splicing 2 (MRS2) (rs7738943: OR = 1.55, FDR-adjusted P = 0.01; rs1056285: OR = 1.48, FDR-adjusted P = 0.02). Even with the most conservative Bonferroni adjustment, two 2-SNP-haplotypes in SLC41A2 and MRS2 region were significantly associated with T2D risk (rs12582312-rs10861279: P = 0.0006; rs1056285-rs7738943: P = 0.002). Among women with magnesium intake in the lowest 30% (AA: <= 0.164 g/d; HA: <= 0.185 g/d), 4 SNP signals were strengthened [rs11590362 in claudin 19 (CLDN19), rs823154 in SLC41A1, rs5929706 and rs5930817 in membra; HA: >= 0.313 g/d), rs6584273 in CNNM1 (OR: 0.71; FDR-adjusted P = 0.04) and rs1800467 in potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) (OR: 2.50; FDR-adjusted P = 0.01) were significantly associated with T2D risk. Conclusions: Our findings suggest important associations between genetic variations in magnesium-related ion channel genes and T2D risk in AA and HA women that vary by amount of magnesium intake.
引用
收藏
页码:418 / 424
页数:7
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