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

<div><p>Context</p><p>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 <i>SP-D</i> with insulin resistance and type 2 diabetes (T2D).</p> <p>Research Design and Methods</p><p>We evaluated a common genetic variant located in the <i>SP-D</i> coding region (rs721917, Met³¹Thr) 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).</p> <p>Results</p><p>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 <i>SP-D</i> genomic region (i.e. rs10887344) were significantly associated with quantitative measures of glucose homeostasis, insulin sensitivity, and T2D, according to GWAS datasets from MAGIC.</p> <p>Conclusions</p><p><i>SP-D</i> gene polymorphisms are associated with insulin resistance and T2D. These associations are independent of circulating SP-D concentrations.</p>