Innate immune gene variation and differential susceptibility to uterine diseases in Holstein cows

An immune response is mounted after binding of Toll-like receptors (TLRs) to pathogen-associated molecular patterns. The primary objective of this study was to test for the associations between bovine single-nucleotide polymorphisms (SNPs) and insertion-deletion (indel) mutations occurring in seven bovine TLR genes (TLRs 1, 2, 4, 5, 6, 9, and 10) that are known to recognize bacterial ligands and the most significant uterine diseases in dairy cows, including metritis (MET), clinical endometritis (CE), and cytologic endometritis (CYE). Custom allele-specific genotyping assays derived from multiple bovine TLR sequencing studies were utilized. Genotypes for 110 loci (SNPs and indels) that are known to be variable in domestic cattle were determined, resulting in 46 monomorphic loci, 64 loci with two alleles, and 35 loci that did not meet our inclusion criterion for minor allele frequency (≥0.10). The association between specific TLR genotypes and each of the uterine diseases (MET, CE, CYE) was evaluated by logistic regression with correction for confounding variables. Collectively, seven SNPs produced uncorrected P values ≤0.05 with respect to three different uterine diseases investigated, but none of the SNP associations endured correction for multiple testing (P values ≥ 0.05). Several confounding variables, including parity, dystocia, and ketosis before 17 DIM, remained significant after correction for multiple testing. Our analysis of these data suggest that some bovine TLR SNPs (i.e., TLRs 2, 4, 6, 9) may potentially elicit relatively small effects on uterine health in Holstein dairy cows and that some confounding variables are actually more predictive for the incidence of disease than any genetic markers evaluated herein.