Genetic variants of major genes contributing to phosphate and calcium homeostasis and their association with serum parameters in pigs

Abstract

Calcium and phosphorus are irreplaceable components of life. Tracking the fate of calcium and phosphorus in organisms deserves high attention due to their relevance in bone metabolism and subsequently animal health. Indeed, bone serves as reservoir for calcium and phosphorus, whose formation and resorption follow specific molecular routes including hormones, receptors, and transcription factors. The objective of the study was to analyze the genetic variation of major components driving mineral utilization such as calcitonin receptor, calcium sensing receptor, fibroblast growth factor 23 (FGF23), parathyroid hormone receptor, osteopontin, stanniocalcin 1, RAF-type zinc finger domain containing 1 (TRAFD1), and vitamin D receptor. A German Landrace pig population (n = 360) was used to perform an association analysis between selected single nucleotide polymorphisms (SNP) and relevant serum parameters (calcium, phosphorus, calcium/phosphorus ratio, alkaline phosphatase). Analyzed SNPs in FGF23 (rs710498025) and TRAFD1 (rs345195312) were significantly (p ≤ 0.05) associated with the serum calcium/phosphorus ratio and serum phosphorus levels, respectively. This might represent a modulation of the homeostatic balance between calcium and phosphorus. Furthermore, TRAFD1 is known to be involved in skeletal disorders which emphasize its link to phosphorus utilization and immune system. However, none of the analyzed genetic variants of these major regulators of phosphate and calcium homeostasis showed significant associations after correction for multiple testing (q value > 0.05). Thus, minor contributors as well as unknown and yet to be elucidated regulators of mineral homeostasis need to be characterized towards the implementation of improved phosphorus efficiency in pig breeding programs.Electronic supplementary materialThe online version of this article (10.1007/s13353-018-0449-2) contains supplementary material, which is available to authorized users.

Genetic Contribution to Variation in Blood Calcium, Phosphorus, and Alkaline Phosphatase Activity in Pigs

“…The proposed list of candidate genes emphasizes that the drivers of Ca and P homeostasis are in fact partly unknown and that several factors remain to be identified. Consistently, a recent study on the genetic contribution of well-known functional candidate genes on Ca and P homeostasis in pigs showed only a small contribution of these major players to the genetic variance (Just et al, 2018b). Further insights into the role of genetics in the regulation of Ca and P homeostasis can be derived from human studies on kidney health and bone metabolism (reviewed by Lederer, 2014).…”

“…Notably, taking into account the QTL intervals derived from a human meta-analysis, at least some functional candidate genes such as CASR , FGF23 , ALPL , and SLC34A1 are included (Kestenbaum et al, 2010). In pigs, even the targeted association analysis of obvious candidate genes involved in Ca and P regulation could not demonstrate significant contributions to the phenotypic variability (Just et al, 2018b). Similarly, in the current GWAS, none of the leading SNPs of the QTL point to positional candidate genes that are hitherto known to be major players in the regulation of Ca and P homeostasis.…”

“…Nevertheless, the current study revealed several QTL regions for the analyzed traits, which partly overlap with genomic regions from pig QTL database. Specifically, porcine genome regions with a contribution to the traits analyzed have been previously mapped on different chromosomes (Supplementary Table 1; Reiner et al, 2009; Yoo et al, 2012; Bovo et al, 2016; Just et al, 2018b). Interestingly, despite the physiological relationship within mineral homeostasis, only few overlapping genomic regions between the individual traits have been identified.…”

“…In addition, RAB35 is a key regulator of intracellular membrane transport and involved in endocytosis. The same QTL on SSC14 further contains the recently proposed candidate gene TRAF-Type Zinc Finger Domain Containing 1 ( TRAFD1 ) (Just et al, 2018b), but also harbors several other genes demanding the dissection of this QTL to provide further insights. Although the genomic region on SSC6 was the most prominent in the multi-marker analysis for IP, the positional candidate genes ( GATA6 and RBBP8 ) lack any connection to P homeostasis so far.…”

“…In pigs of the same age, the Ca and P levels in the blood differ considerably between different breeds or even within breeds, suggesting a genetic contribution to the variability of mineral concentrations (Rodehutscord, 2001; Hittmeier et al, 2006; Just et al, 2018b). However, reliable heritability estimates for the blood values of Ca and P for pigs are not yet available.…”