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Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels.

Publication ,  Journal Article
Qi, Q; Menzaghi, C; Smith, S; Liang, L; de Rekeneire, N; Garcia, ME; Lohman, KK; Miljkovic, I; Strotmeyer, ES; Cummings, SR; Kanaya, AM; Qi, L ...
Published in: Hum Mol Genet
November 1, 2012

Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses' Health Study (n = 1590) and the Health, Aging and Body Composition Study (n = 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n = 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P = 6.37 × 10(-12)) and SNP rs13144478 (P = 6.19 × 10(-18)), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P = 3.68 × 10(-7)). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P = 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio = 1.18 (95% CI, 1.03-1.34); P = 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease.

Duke Scholars

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

November 1, 2012

Volume

21

Issue

21

Start / End Page

4774 / 4780

Location

England

Related Subject Headings

  • zeta-Crystallins
  • White People
  • Sulfotransferases
  • Resistin
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Membrane Proteins
  • Insulin Resistance
  • Humans
 

Citation

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ICMJE
MLA
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Qi, Q., Menzaghi, C., Smith, S., Liang, L., de Rekeneire, N., Garcia, M. E., … Qi, L. (2012). Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels. Hum Mol Genet, 21(21), 4774–4780. https://doi.org/10.1093/hmg/dds300
Qi, Qibin, Claudia Menzaghi, Shelly Smith, Liming Liang, Nathalie de Rekeneire, Melissa E. Garcia, Kurt K. Lohman, et al. “Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels.Hum Mol Genet 21, no. 21 (November 1, 2012): 4774–80. https://doi.org/10.1093/hmg/dds300.
Qi Q, Menzaghi C, Smith S, Liang L, de Rekeneire N, Garcia ME, et al. Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels. Hum Mol Genet. 2012 Nov 1;21(21):4774–80.
Qi, Qibin, et al. “Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels.Hum Mol Genet, vol. 21, no. 21, Nov. 2012, pp. 4774–80. Pubmed, doi:10.1093/hmg/dds300.
Qi Q, Menzaghi C, Smith S, Liang L, de Rekeneire N, Garcia ME, Lohman KK, Miljkovic I, Strotmeyer ES, Cummings SR, Kanaya AM, Tylavsky FA, Satterfield S, Ding J, Rimm EB, Trischitta V, Hu FB, Liu Y, Qi L. Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels. Hum Mol Genet. 2012 Nov 1;21(21):4774–4780.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

November 1, 2012

Volume

21

Issue

21

Start / End Page

4774 / 4780

Location

England

Related Subject Headings

  • zeta-Crystallins
  • White People
  • Sulfotransferases
  • Resistin
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Membrane Proteins
  • Insulin Resistance
  • Humans