Association of leptin gene polymorphisms with serum leptin concentration in dairy cows

Abstract

Leptin is a hormone produced by adipocytes, and its expression is regulated by body fatness and energy balance. This study describes the association of four leptin gene polymorphisms in dairy cows (R4C, A59V, RFLP1, and BM1500) with circulating leptin concentrations during the periparturient period. A59V is located at a between-species conserved region of leptin, and R4C might have effect on the tertiary structure of the leptin protein because of the presence of an extra cystein. RFLP1 is an intronic SNP and BM1500 is a microsatellite located 3.6 kb downstream of the leptin locus. The four polymorphisms were genotyped in 323 HF heifers with known pedigree. Leptin concentrations were determined biweekly from 30 days before until 80 days after parturition. The effect of genotype on leptin concentrations was modeled by fitting a spline in ASREML describing leptin concentrations as a function of days relative to parturition for each genotype/allele. Surprisingly, associations were found during pregnancy, but not during lactation. This indicates that the polymorphism could be more effective during pregnancy. If further studies demonstrate that more leptin-binding protein (Ob-Re) is present in this stage, it is hypothesized that a structural difference in the leptin protein could cause a sub-optimal binding stringency to Ob-Re. Free leptin could be cleared faster than bound leptin, and this could result in lower leptin concentrations during pregnancy for the polymorphism. The effects found might be ascribed to R4C. However, more study on the Ob-Re receptor, like binding stringencies between R4C and wild-type leptin and glycosylation during pregnancy, would provide more insight in the results found.

Impact of leptin gene polymorphisms on breeding value for milk production traits in cattle

“…On the other hand, the observed negative effect on fat percentage could be simply a consequence of the higher milk yield without simultaneously increased amount of produced fat. The investigations on Dutch heifers (Liefers et al, 2003;Liefers, 2004) and British experimental population (Lagonigro et al, 2003) provided more arguments against the hypothesis postulated by Buchanan et al (2002). Liefers et al (2003) obtained results suggesting that not the TT, but the CC genotype is characterized by a higher circulating leptin concentration.…”

“…The physiological properties, as well as the effects of the mouse ob locus variants support leptin as a strong candidate gene that could influence production traits in farm animals. In cattle, several studies have indicated an association between leptin gene polymorphisms and feed intake and carcass fat content, although reproduction and milk related traits were proved to be also affected (Fitzsimmons et al, 1998;Zwierzchowski et al, 2001;Liefers et al, 2002Liefers et al, , 2003. Buchanan et al (2002) proposed the C/T substitution in exon 2 that causes amino acid change from Arg to Cys at position 4 of the leptin protein (Arg4Cys) as a causative mutation affecting fat carcass content in cattle.…”

“…It consists of three exons, with the coding regions in exon 2 and exon 3. Several polymorphims have been reported in the bovine leptin gene, but only four of them change the amino acid sequence in the encoding polypeptide (Konfortov et al, 1999;Haegeman et al, 2000;Buchanan et al, 2002;Lagonigro et al, 2003;Liefers et al, 2003). Recently, the promoter region has been sequenced and twenty SNPs (single nucleotide polymorphisms) have been found (Liefers, 2004).…”

“…The Arg4Cys is the C → T substitution located 73 bp from the start of exon 2 that causes amino acid change from arginine to cysteine at position 4 of the mature leptin (Konfortov et al, 1999;Buchanan et al, 2002;Lagonigro et al, 2003;Liefers et al, 2003), whereas the Ala59Val is the C → T mutation located 95 bp from the start of exon 3 leading to the alanine → valine change at protein position 59 (Konfortov et al, 1999;Haegeman et al, 2000;Buchanan et al, 2002;Lagonigro et al, 2003;Liefers et al, 2003).…”

Genetic polymorphisms at the leptin receptor gene in three beef cattle breeds

“…Almeida et al 683 Many genetic and environmental factors influence reproductive performance and weight gain, with each individual gene having a small effect. As a matter of fact, mutations in other genes, mainly in leptin, are being described as affecting cattle weight gain and reproduction (Almeida et al, 2003(Almeida et al, , 2007Liefers et al, 2002Liefers et al, , 2003Liefers et al, , 2005.…”