Human ADRB2 blocking peptide

The aim of this study was to investigate 96 single-nucleotide polymorphisms (SNPs) from 54 candidate genes, and test the associations of the polymorphic SNPs with milk yield, composition, milk urea nitrogen (MUN) content and somatic cell score (SCS) in individual milk samples from Italian Brown Swiss cows. Milk and blood samples were collected from 1271 cows sampled once from 85 herds. Milk production, quality traits (i.e. protein, casein, fat and lactose percentages), MUN and SCS were measured for each milk sample. Genotyping was performed using a custom Illumina VeraCode GoldenGate approach. A Bayesian linear animal model that considered the effects of herd, days in milk, parity, SNP genotype and additive polygenic effect was used for the association analysis. Our results showed that 14 of the 51 polymorphic SNPs had relevant additive effects on at least one of the aforementioned traits. Polymorphisms in the glucocorticoid receptor DNA-binding factor 1 (GRLF1), prolactin receptor (PRLR) and chemokine ligand 2 (CCL2) were associated with milk yield; an SNP in the stearoyl-CoA desaturase (SCD-1) was related to fat content; SNPs in the caspase recruitment domain 15 protein (CARD15) and lipin 1 (LPIN1) affected the protein and casein contents; SNPs in growth hormone 1 (GH1), lactotransferrin (LTF) and SCD-1 were relevant for casein number; variants in beta casein (CSN2), GH1, GRLF1 and LTF affected lactose content; SNPs in beta-2 adrenergic receptor (ADRB2), serpin peptidase inhibitor (PI) and SCD-1 were associated with MUN; and SNPs in acetyl-CoA carboxylase alpha (ACACA) and signal transducer and activator of transcription 5A (STAT5A) were relevant in explaining the variation of SCS. Although further research is needed to validate these SNPs in other populations and breeds, the association between these markers and milk yield, composition, MUN and SCS could be exploited in gene-assisted selection programs for genetic improvement purposes.

Background: Sudden cardiac arrest has been linked independently both to stressful neighborhood conditions and to polymorphisms in the ADRB2 gene. The ADRB2 gene mediates sympathetic activation in response to stress. Therefore, if neighborhood conditions cause cardiac arrest through the stress pathway, the ADRB2 variant may modify the association between neighborhood conditions, such as socioeconomic deprivation and incidence of cardiac arrest. Methods: The Cardiac Arrest Blood Study Repository is a population-based repository of specimens and other data from adult cardiac arrest patients residing in King County, Washington. Cases (n = 1,539) were 25-to 100-year-old individuals of European descent who experienced out-of-hospital cardiac arrest from 1988 to 2004. Interactions between neighborhood conditions and the ADRB2 genotype on cardiac arrest risk were assessed in a case-only study design. Gene-environment independence was assessed in blood samples obtained from King County residents initially contacted by randomdigit dialing. Results: Fewer than 4% of study subjects resided in socioeconomically deprived neighborhoods. Nonetheless, the case-only analysis indicated the presence of supramultiplicative interaction of socioeconomic deprivation and the homozygous Gln27Glu variant (caseonly odds ratio: 1.8 [95% confidence interval: 1.0, 2.9]). Interactions between population density and the homozygous Gln27Glu variant were weaker (case-only odds ratio: 1.2 [95% confidence interval: 0.97, 1.5]). Conclusions: Findings support a supramultiplicative interaction between the Gln27Glu ADRB2 variant and socioeconomic deprivation among individuals of European descent. This result is consistent with the hypothesis that the elevation in cardiac arrest risk associated with socioeconomic deprivation operates through the stress pathway.