title: Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes.
abstract: BACKGROUND
  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).
  
  
  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.
authors.affiliation: Service of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn, CB06/03/0010) and Instituto de Salud Carlos III (ISCIII), Girona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Pueyo
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Ortega
authors.forename: Josep M
authors.initials: JM
authors.lastname: Mercader
authors.forename: José M
authors.initials: JM
authors.lastname: Moreno-Navarrete
authors.forename: Monica
authors.initials: M
authors.lastname: Sabater
authors.forename: Sílvia
authors.initials: S
authors.lastname: Bonàs
authors.forename: Patricia
authors.initials: P
authors.lastname: Botas
authors.forename: Elías
authors.initials: E
authors.lastname: Delgado
authors.forename: Wifredo
authors.initials: W
authors.lastname: Ricart
authors.forename: María T
authors.initials: MT
authors.lastname: Martinez-Larrad
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano-Ríos
authors.forename: David
authors.initials: D
authors.lastname: Torrents
authors.forename: José M
authors.initials: JM
authors.lastname: Fernández-Real
mesh_terms: D030541:Databases, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood / Q000235:genetics*
chemical_list: D037663:Pulmonary Surfactant-Associated Protein D