title: Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci associated with circulating resistin levels.
abstract: 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.
authors: Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors: Qibin
authors: Q
authors: Qi
authors: Claudia
authors: C
authors: Menzaghi
authors: Shelly
authors: S
authors: Smith
authors: Liming
authors: L
authors: Liang
authors: Nathalie
authors: N
authors: de Rekeneire
authors: Melissa E
authors: ME
authors: Garcia
authors: Kurt K
authors: KK
authors: Lohman
authors: Iva
authors: I
authors: Miljkovic
authors: Elsa S
authors: ES
authors: Strotmeyer
authors: Steve R
authors: SR
authors: Cummings
authors: Alka M
authors: AM
authors: Kanaya
authors: Frances A
authors: FA
authors: Tylavsky
authors: Suzanne
authors: S
authors: Satterfield
authors: Jingzhong
authors: J
authors: Ding
authors: Eric B
authors: EB
authors: Rimm
authors: Vincenzo
authors: V
authors: Trischitta
authors: Frank B
authors: FB
authors: Hu
authors: Yongmei
authors: Y
authors: Liu
authors: Lu
authors: L
authors: Qi
mesh_terms: D000328:Adult; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics; D052243:Resistin / Q000097:blood / Q000235:genetics*; D015238:Sulfotransferases / Q000235:genetics*; D044465:White People / Q000235:genetics; D038226:zeta-Crystallins / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D052243:Resistin; D038226:zeta-Crystallins; D015238:Sulfotransferases; C422953:NDST4 protein, human