Leptin Gene Polymorphism Research Articles

P.3.c.043 Association of leptin gene polymorphism with antipsychotic drug-induced weight gain

P.3.c.043 Association of leptin gene polymorphism with antipsychotic drug-induced weight gain

DNA polymorphism of leptin gene in Bos indicus and Bos taurus cattle

Leptin plays an important role in the regulation of feed intake, energy metabolism, growth and reproduction of cattle. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique to screen for DNA polymorphisms of the leptin gene in 403 cattle belonging to various breeds of Bos indicus (Hariana, Sahiwal, Gir and Nimari cattle), Bos taurus (Holstein Friesian (HF) and Jersey cattle) as well as Bos taurus x Bos indicus crossbreds (½ HF x ½ Hariana). In all the cattle we amplified two regions of the leptin gene, a 522 bp fragment comprising the partial intron 2 and exon 3 and another 94 bp fragment consisting of part of exon 2. Digestion of 522 bp PCR products with the BsaAI restriction enzyme revealed three genotypes in all the breeds of cattle studied. This is the first report of the presence of leptin gene polymorphism in purebred Bos indicus cattle of Indian origin (indicine cattle). Almost similar gene and genotype frequencies were observed in all the breed groups, while the frequency of mutant homozygotes (AA) was very low (0.03 to 0.07). On digestion of the 94 bp fragment with the Kpn2I restriction enzyme, three genotypes were observed in HF, Jersey and crossbred cattle. The CC genotype had the highest frequency (0.68) in crossbreds whereas the frequency of CT heterozygotes was highest (0.69) in HF cattle. This mutation was absent in all the breeds of indicine cattle. The results suggest that the BsaAI-RFLP mutation has occurred far back in evolution before the divergence of taurine and indicine cattle while the Kpn2I mutation has occurred recently as indicated by the fact that this mutation was only detected in taurine cattle.

Microsatellite polymorphism of the human leptin gene (LEP) and risk of cardiovascular disease

No data have been so far reported on the relationship between polymorphisms of LEP gene and cardiovascular disease. We genotyped a tetranucleotide repeat mapped in the 3'UTR of the LEP gene (LEP-tet) in 109 subjects with cardiovascular events and in 109 control subjects. Univariate analysis and multivariate logistic regression analysis adjusted for age, gender, smoking status, history of hyperlipidemia, hypertension or diabetes showed not significant association between the genotype of the LEP-tet and cardiovascular diseases. Moreover, no differences were observed in the plasma leptin concentrations between cases and control subjects (22 +/- 19 vs 22 +/- 14 ng/ml, P = 0.52) and in relation to the LEP-tet classes or carriage of specific alleles (P = 0.76 for the association between LEP-tet classes and leptin levels in overall analysis). In conclusion, our data do not support an association between the LEP-tet microsatellite polymorphism of the human LEP gene and cardiovascular diseases.

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

1. Practical application of daughter yield deviations in dairy cattle breeding Joanna Szyda, Ewa Ptak, Jolanta Komisarek, Andrzej Żarnecki Journal of Applied Genetics CrossRef

Associations between leptin gene polymorphism and some milk performance traits of cattle

Associations between leptin gene polymorphism and some milk performance traits of cattle

Genetics and physiology of leptin in periparturient dairy cows

In dairy cattle, the increase in milk yield has been accompanied by a more negative energy balance (EB) during early lactation and a decrease in fertility. As the hormone leptin is involved in regulation of nutritional status and reproductive function this hormone is an interesting protein to investigate during the periparturient period in dairy cattle. This study was performed to get insight into the function of leptin during the periparturient period and to perform an association study between polymorphisms in the bovine leptin gene and leptin receptor gene and fertility as well as production traits. Leptin concentrations in the periparturient cow undergo remarkable changes; leptin concentrations were high during late pregnancy and declined to a nadir at parturition. Genetic analysis of the leptin gene indicated that a combination of three polymorphisms located at a 135 bp region of the leptin promoter explained most of the variance in prepartum leptin concentrations. The two extreme genotype combinations could be used to investigate the function of leptin concentrations in pregnant cows. A polymorphism located on intron 2 of the leptin gene explained a significant part of the variation in milk yield. On the promoter region of the leptin gene an SNP was detected that was associated with first postpartum luteal activity (FPLA). This SNP could be a candidate marker for fertility in dairy cows. Another SNP on the leptin promoter was associated with energy balance and dry matter intake (DMI) where a higher dry matter intake occurred together with a higher energy balance. Two genotype combinations of the aforementioned three associated SNPs were defined which had a good milk yield together with a good energy balance and fertility. Calculations of an economical value per trait have to validate if one of these genotype combinations would be a possible candidate to be used in selection.

Leptin, soluble leptin receptor and leptin gene polymorphism in relation to preeclampsia risk.

Few investigators have simultaneously evaluated leptin, soluble leptin receptor (SLR) and leptin gene polymorphisms in preeclampsia cases and controls. We examined these three biomolecular markers in 40 preeclampsia cases and 39 controls. Plasma leptin and SLR concentrations were determined using immunoassays. Genotype for the tetranucleotide repeat (TTTC)(n), polymorphism in the 3 -flanking region of the leptin gene was determined using PCR. Alleles of the polymorphism were characterized by size distributions [short repeats (class I); and long repeats (class II)]. Logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI). Leptin concentrations were higher in our cases than in the controls (53.1 4.7 vs. 17.7+/-2.4 ng/ml, p<0.05). SLR concentrations were slightly lower in our patients than in the controls (25.7+/-1.9 vs. 29.1+/-1.1 ng/ml, p>0.05). Elevated leptin (? 14.5 ng/ml) was associated with a 3.8-fold (CI 1.0-14.4) increased risk; whereas low SLR (< 28.5 ng/ml) was associated with a 6.3-fold (CI 1.7-23.2) increased risk of preeclampsia. The I/II genotype was associated with a 3.8-fold increased risk of preeclampsia (OR=3.8; 95 % CI 0.8-18.0); and the II/II genotype was not observed among our cases (0 % vs. 33 % p<0.001). Larger studies would be needed to confirm and further clarify the relations between functional variants in the leptin gene and preeclampsia risk.

Association of a single nucleotide polymorphism in the bovine leptin gene with feed intake, feed efficiency, growth, feeding behaviour, carcass quality and body composition

Leptin is a 16-kDa-hormone product of the obese gene synthesized and expressed predominantly by adipose tissues, which has been shown to play major roles in the regulation of body weight, feed intake, energy balance, fertility, and immune system functions. We report an investigation into the association of a previously identified cytosine to thymine missense mutation in exon 2 of the bovine leptin gene with feed intake, feed efficiency, growth, feeding behaviour, carcass quality and body composition in five genetic selection lines of a commercial population of beef cattle. Differences among genotypes in growth, feed intake and feed efficiency were not significant (P &gt; 0.10) though steers homozygous for the thymine allele had positive residual feed intake (i.e., consumed more feed than expected) (+ 0.19 kg d-1) whilst steers homozygous for the cytosine allele had negative residual feed intake (-0.18 kg d-1). Steers carrying the thymine allele had a higher rate of gain in ultrasound backfat (P = 0.02), ultrasound backfat thickness (P = 0. 06), higher carcass grade fat (backfat) (P = 0.005), lower yield grade (P = 0.01) and lower lean meat yield (P = 0.007). The thymine allele also tended to be associated with higher loin subcutaneous fat (P = 0.07) and was associated with higher brisket subcutaneous fat (P = 0.01), and brisket body cavity fat (P = 0.0001). No associations were found among the different genotypes and real-time ultrasound marbling, ultrasound longissimus thoracis area, carcass marbling and carcass longissimus thoracis area (P &gt; 0.10). Our results show that animals carrying the thymine allele versus the cytosine allele may produce carcasses with poorer grades and lower lean meat yields but do not differ in carcass marbling or other fat depots. Key words: Beef cattle, leptin, feed intake, carcass merit

Genetic polymorphisms in porcine leptin gene and their association with reproduction and production traits

Leptin (LEP), the product of the leptin gene, is a 16-kDa protein synthesised by adipose tissue and is involved in regulation of feed intake, energy balance, fertility, and immune functions. Using bi-directional polymerase chain reaction amplification of specific alleles (bi-PASA) and PCR-restriction fragment length polymorphisms (PCR-RFLP), we have successfully detected genetic polymorphisms of LEP intron 1 and exon 3, respectively, in Landrace, Yorkshire, and Duroc. Chi-square statistics were used to calculate homogeneity of genotypic frequencies of 2 candidate genes for 3 breeds of animals. Effects of exon 3 polymorphisms on reproduction traits such as litter sizes of sows in the first parity and 1–4 parities were evident (P &lt; 0.05) in Landrace, and 1–4 parities in Yorkshire. Polymorphisms of intron 1 affected (P &lt; 0.05) only litter sizes of the first parity in Duroc. Effects of exon 3 polymorphisms on production traits such as average daily gain and feed efficiency were evident (P &lt; 0.05) in Landrace and Yorkshire, respectively. Polymorphisms of intron 1 affected (P &lt; 0.05) only backfat thickness in Duroc. Our data also show that the higher the reproduction traits, the lower the genotypic frequencies. Further, the better the production traits, the higher the genotypic frequencies were. These data suggest that the long-term selection of favourable traits in pig production may be partially attributed to the effects of LEP polymorphisms on reproduction and production traits.

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

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.

Leptin gene polymorphism is associated with hypertension independent of obesity.

Leptin is an adipocyte-derived hormone that regulates food intake and energy expenditure. Recent functional studies have suggested a direct effect of leptin on blood pressure. In this study we examined the genetic association of the leptin gene polymorphism with obesity, insulin resistance, and hypertension. A highly polymorphic tetranucleotide repeat polymorphism in the 3'-flanking region of the leptin gene was examined. The alleles of the polymorphism consisted of two groups with different size distributions: a shorter one (class I) and a longer one (class II). The frequency of class I/class I genotype was much higher in hypertensive subjects than in control subjects (13.5% vs. 3.4%; P = 0.0027). No significant difference in body mass index was observed with different genotypes in either patients with hypertension or control subjects. Insulin responses to glucose and insulin sensitivity were not different among patients with different genotypes. The leptin gene polymorphism was associated with hypertension independent of obesity. These data together with recent functional data on the direct effect of leptin on blood pressure suggest that the leptin gene and its product, leptin, are an attractive target for studies on the mechanisms of hypertension and for the development of methods for the prediction, prevention, and therapy for hypertension.

Associations between Leptin Gene Polymorphisms and Production, Live Weight, Energy Balance, Feed Intake, and Fertility in Holstein Heifers

Leptin is a 16-kDa protein synthesized by adipose tissue and is involved in regulation of feed intake, energy balance, fertility, and immune functions. Since evidence of a genetic correlation between start of luteal activity and energy balance, milk yield, and live weights is present, we investigated the association of genetic differences in the bovine leptin gene with these traits. Between 1990 and 1997, a total of 613 Holstein-Friesian heifers of two genetic groups with known pedigree were followed from parturition until d 105 of lactation. During the first 15 wk of lactation live weight, feed intake, and milk yield were measured for 565 cows. The start of luteal activity was set at the first day with a progesterone concentration higher than 3ng/ml. In addition to the interval between calving and start of luteal activity, analyses were performed for average milk yield, percentage fat, protein, and lactose in milk, dry matter intake, feed intake, energy balance, and live weight over the first 15 wk of lactation. All 613 cows were genotyped for two restricted fragment length polymorphisms and for the BM1500 microsatellite, all located at the leptin gene locus. Significances of the genotype effects were estimated using the approximated F-statistic provided by ASREML. Fixed effects were year-season, genetic group, and a quadratic polynomial for age at calving. Animal was fitted as a random effect including the additive relationship between animals to account for background genes. Firstly, each genotype effect was fitted in turn, and secondly the other restriction fragment length polymorphisms were fitted as a cofactor to take into account effects of linkage disequilibrium. Thirdly, sire × genotype interaction was investigated.Heifers with the RFLP1-AB genotype produce 1.32 kg/d more milk and consume 0.73 kg/d more food compared with the RFLP1-AA genotype. No effects were found for start of luteal activity. When linkage disequilibrium with the other markers was taken into account and DMI was included as fixed effect in the model a 0.96 kg/d higher milk yield was still found. Assuming that no pleiotropic effects on traits such as immunity and milk production in later lactations exist, future breeding programs favoring the RFLP1 B-allele can yield a higher milk production without negatively affecting energy balance and fertility. The prospects are good because in this study the frequency of the RFLP1 AB- and BB-genotypes were only 18.5 and 0.2%, respectively.

Leptin Gene Polymorphism Is Associated with Hypertension Independent of Obesity

Leptin Gene Polymorphism Is Associated with Hypertension Independent of Obesity

Effect of leptin gene polymorphism on growth and carcass traits in pigs (short communication)

Abstract. The polymorphism of the porcine leptin gene and its relation with some Performance traits (body weight, average daily gains, lean meat content) were analysed in 131 sows of Polish Landrace. The frequencies of detected genotypes TT, TC and CC were 0.763, 0.222 and 0.015 respectively. The estimated frequencies of alleles were 0.874 for allele T and 0,126 for allele C. Lean meat content and average daily gains in TC pigs were statistically significantly higher then those of TT individuals. No statistically significant differences in body weight were found among sows of the above genotypes.

Characterization of swine leptin (LEP) polymorphisms and their association with production traits.

Four polymorphisms in the swine leptin (LEP) gene were characterized and evaluated for association with economically important production traits in Yorkshire, Landrace and Duroc pigs. Our results show that these polymorphisms are generally of low frequency or are absent in pig populations. Two polymorphisms (A2845T and T3469C) may be associated (P < 0.0078) with feed intake and growth rate traits in Landrace pigs.

Vitamins and Hormones. Advances in Research and Applications

1. Neuroendocrine and Behavioral Development During Puberty: A Tale of Two 2. Regulation of Oxytocin Secretion 3. Gonadotropin- Releasing Hormone: Gene Evolution, Expression and Regulation 4. Thyroid Hormones and Brain Development 5. Estrogen signaling in the Hypothalamus 6. Hormonal Influences on Cancer Progression and Prognosis 7. Antiestrogens, Aromatase Inhibitors, and Apoptosis in Breast Cancer 8. Glucocorticoid Receptor and Heat Shock Factor-1: Novel Mechanisms of Reciprocal Regulation 9. C19-5-ene Steroids in Nature 10. The Androgen Receptor: Unlocking the Secrets of its Unique Transactivation Domain 11. Cytokine Recognition by the Human Interleukin-5 Receptor 12. Leptin: Structure, Function and Biology 13. Leptin Gene Polymorphisms and their Phenotypic Associations 14. Ghrelin, the Same Peptide for Different Functions: Player or Bystander? 15. Cholecystokinin (CCK) and Adrenal-Cortex Secretion

Vitamins and Hormones. Advances in Research and Applications.

1. Neuroendocrine and Behavioral Development During Puberty: A Tale of Two 2. Regulation of Oxytocin Secretion 3. Gonadotropin- Releasing Hormone: Gene Evolution, Expression and Regulation 4. Thyroid Hormones and Brain Development 5. Estrogen signaling in the Hypothalamus 6. Hormonal Influences on Cancer Progression and Prognosis 7. Antiestrogens, Aromatase Inhibitors, and Apoptosis in Breast Cancer 8. Glucocorticoid Receptor and Heat Shock Factor-1: Novel Mechanisms of Reciprocal Regulation 9. C19-5-ene Steroids in Nature 10. The Androgen Receptor: Unlocking the Secrets of its Unique Transactivation Domain 11. Cytokine Recognition by the Human Interleukin-5 Receptor 12. Leptin: Structure, Function and Biology 13. Leptin Gene Polymorphisms and their Phenotypic Associations 14. Ghrelin, the Same Peptide for Different Functions: Player or Bystander? 15. Cholecystokinin (CCK) and Adrenal-Cortex Secretion