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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.

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