Common Genetic Variants of Surfactant Protein-D (SP-D) Are Associated with Type 2 Diabetes

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Output type: Journal article

Author list: Pueyo N., Ortega F., Mercader J., Moreno-Navarrete J., Sabater M., Bonàs S., Botas P., Delgado E., Ricart W., Martinez-Larrad M., Serrano-Ríos M., Torrents D., Fernández-Real J.

Publisher: Public Library of Science

Publication year: 2013

Journal: PLoS ONE (1932-6203)

Journal acronym: PLOS ONE

Volume number: 8

Issue number: 4

ISSN: 1932-6203

eISSN: 1932-6203

URL: http://api.elsevier.com/content/abstract/scopus_id:84875946684

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Open access status: gold

Full text URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0060468&type=printable

Abstract

Context: Surfactant protein-D (SP-D) is a primordial component of the innate immune system intrinsically linked to metabolic pathways. We aimed to study the association of single nucleotide polymorphisms (SNPs) affecting SP-D with insulin resistance and type 2 diabetes (T2D). Research Design and Methods: We evaluated a common genetic variant located in the SP-D coding region (rs721917, MetThr) in a sample of T2D patients and non-diabetic controls (n = 2,711). In a subset of subjects (n = 1,062), this SNP was analyzed in association with circulating SP-D concentrations, insulin resistance, and T2D. This SNP and others were also screened in the publicly available Genome Wide Association (GWA) database of the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). Results: We found the significant association of rs721917 with circulating SP-D, parameters of insulin resistance and T2D. Indeed, G carriers showed decreased circulating SP-D (p = 0.004), decreased fasting glucose (p = 0.0002), glycated hemoglobin (p = 0.0005), and 33% (p = 0.002) lower prevalence of T2D, estimated under a dominant model, especially among women. Interestingly, these differences remained significant after controlling for origin, age, gender, and circulating SP-D. Moreover, this SNP and others within the SP-D genomic region (i.e. rs10887344) were significantly associated with quantitative measures of glucose homeostasis, insulin sensitivity, and T2D, according to GWAS datasets from MAGIC. Conclusions: SP-D gene polymorphisms are associated with insulin resistance and T2D. These associations are independent of circulating SP-D concentrations. © 2013 Pueyo et al.

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