Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes

PLoS One. 2013;8(4):e60468. doi: 10.1371/journal.pone.0060468. Epub 2013 Apr 5.


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, Met(31)Thr) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Insulin Resistance / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Pulmonary Surfactant-Associated Protein D / blood
  • Pulmonary Surfactant-Associated Protein D / genetics*


  • Pulmonary Surfactant-Associated Protein D

Grant support

This work was supported by research grants from the Spanish Ministry of Science and Innovation (FIS 2011-0214), CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn), and by research grants from the Spanish Ministry of Science and Education (SAF 2005-02073). Dr. Josep M. Mercader was supported by Sara Borrell fellowship from the Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.