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

Kei Hang K Chan, Sara A. Chacko, Yiqing Song, Michele Cho, Charles B. Eaton, Wen Chih H. Wu, Simin Liu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 cyclinmediator 1 (CNNM1) had 16% lower T2D risk [OR: 0.84; false discovery rate (FDR)-adjusted P= 0.02]. Among HA women, several variantswere significantly associatedwith 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 P50.04), and 2 SNPs in mitochondrial RNA splicing 2 (MRS2) (rs7738943: OR = 1.55, FDR-adjusted P = 0.01; rs1056285: OR 5 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.

Original languageEnglish (US)
Pages (from-to)418-424
Number of pages7
JournalJournal of Nutrition
Volume145
Issue number3
DOIs
StatePublished - Jan 1 2015

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Ion Channels
Hispanic Americans
African Americans
Magnesium
Type 2 Diabetes Mellitus
Single Nucleotide Polymorphism
RNA Splicing
Haplotypes
Chloride-Bicarbonate Antiporters
Angelman Syndrome
Genes
Inwardly Rectifying Potassium Channel
Prader-Willi Syndrome
Social Adjustment
Health Resources
Women's Health
Homeostasis
Prospective Studies

Keywords

  • Diabetes
  • Genes
  • Ion channel
  • Magnesium intake
  • Women

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and hispanic American women. / K Chan, Kei Hang; Chacko, Sara A.; Song, Yiqing; Cho, Michele; Eaton, Charles B.; Wu, Wen Chih H.; Liu, Simin.

In: Journal of Nutrition, Vol. 145, No. 3, 01.01.2015, p. 418-424.

Research output: Contribution to journalArticle

K Chan, Kei Hang ; Chacko, Sara A. ; Song, Yiqing ; Cho, Michele ; Eaton, Charles B. ; Wu, Wen Chih H. ; Liu, Simin. / Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and hispanic American women. In: Journal of Nutrition. 2015 ; Vol. 145, No. 3. pp. 418-424.
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title = "Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and hispanic American women",
abstract = "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 cyclinmediator 1 (CNNM1) had 16{\%} lower T2D risk [OR: 0.84; false discovery rate (FDR)-adjusted P= 0.02]. Among HA women, several variantswere significantly associatedwith 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 P50.04), and 2 SNPs in mitochondrial RNA splicing 2 (MRS2) (rs7738943: OR = 1.55, FDR-adjusted P = 0.01; rs1056285: OR 5 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.",
keywords = "Diabetes, Genes, Ion channel, Magnesium intake, Women",
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doi = "10.3945/jn.114.203489",
language = "English (US)",
volume = "145",
pages = "418--424",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
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TY - JOUR

T1 - Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and hispanic American women

AU - K Chan, Kei Hang

AU - Chacko, Sara A.

AU - Song, Yiqing

AU - Cho, Michele

AU - Eaton, Charles B.

AU - Wu, Wen Chih H.

AU - Liu, Simin

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 cyclinmediator 1 (CNNM1) had 16% lower T2D risk [OR: 0.84; false discovery rate (FDR)-adjusted P= 0.02]. Among HA women, several variantswere significantly associatedwith 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 P50.04), and 2 SNPs in mitochondrial RNA splicing 2 (MRS2) (rs7738943: OR = 1.55, FDR-adjusted P = 0.01; rs1056285: OR 5 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.

AB - 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 cyclinmediator 1 (CNNM1) had 16% lower T2D risk [OR: 0.84; false discovery rate (FDR)-adjusted P= 0.02]. Among HA women, several variantswere significantly associatedwith 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 P50.04), and 2 SNPs in mitochondrial RNA splicing 2 (MRS2) (rs7738943: OR = 1.55, FDR-adjusted P = 0.01; rs1056285: OR 5 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.

KW - Diabetes

KW - Genes

KW - Ion channel

KW - Magnesium intake

KW - Women

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