Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and Hispanic American women

• Published in: The Journal of nutrition Vol. 145; no. 3; pp. 418 - 424
• Main Authors: Chan, Kei Hang K, Chacko, Sara A, Song, Yiqing, Cho, Michele, Eaton, Charles B, Wu, Wen-Chih H, Liu, Simin
• Format: Journal Article
• Language: English
• Published: United States 01.03.2015
• Subjects: Aged; Black or African American - genetics; Body Mass Index; Case-Control Studies; Cation Transport Proteins - genetics; Claudins - genetics; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Dietary Supplements; Female; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotyping Techniques; Haplotypes; Hispanic or Latino - genetics; Humans; Ion Channels - genetics; Logistic Models; Magnesium - administration & dosage; Magnesium - blood; Middle Aged; Polymorphism, Single Nucleotide; Postmenopause; Potassium Channels, Inwardly Rectifying - genetics; Prospective Studies; Risk Factors; magnesium intake; genes; ion channel; diabetes; women
• ISSN: 0022-3166; 1541-6100
• DOI: 10.3945/jn.114.203489

Prospective studies consistently link low magnesium intake to higher type 2 diabetes (T2D) risk. 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. 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. 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. 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.