Leptin Polymorphisms Research Articles

Association of polymorphism of some candidate genes of lipid and carbohydrate metabolism with anthropometric indices and inflammatory markers in patients with type 2 diabetes mellitus in the population of Azerbaijan

The purpose of the study was to analyze the association of gene polymorphisms of leptin, adiponectin, tumor necrosis factor alpha (TNF-α), insulin-induced gene, and the parameters of carbohydrate and lipid metabolism, level of C-reactive protein (CRP) in patients with type 2 diabetes mellitus (T2DM) with anthropometric data. A total of 95 patients with T2DM of Azerbaijan population. The average age at the time of the survey was 50,4±0,51 years. Duration of the disease was 5,8±1,5 years. We found that patients with T2DM and obesity in the Azerbaijan population have most common polymorphism of insulin-induced gene in the homozygous form (GG), a mutant version of the gene in heterozygous form of leptin, adiponectin gene mutant variant in homozygous form and the normal version of the gene TNF-α in homozygous form. In 47.3% of cases there was a high level of CRP, a linear body mass index with normal homozygous GG allele of the TNF-a gene , insulin-induced gene, and a mutant version of the adiponectin and leptin genes.

Synergistic effect of LEP and LEPR gene polymorphism on body mass index in a Chinese population

Both leptin (LEP) and leptin receptor (LEPR) are important in the regulation of body weight. In this study, we evaluated the individual and combined effects of a polymorphic microsatellite marker in the LEP gene 3' flanking region and two polymorphisms (Lys109Arg and Lys656Asn) of the LEPR gene on metabolic markers for obesity in a Chinese population. The genotypes of polymorphisms in LEP and LEPR gene were determined by PCR and SSCP assay in 230 simple obese subjects and 202 control subjects of Chinese population. Logistic regression analysis showed that polymorphism in LEP gene 3' flanking region was associated with waist/hip ratio (WHR) (P = 0.042). Individually, Lys109Arg variant in LEPR gene was associated with systolic blood pressure (P = 0.031) in males, and Lys656Asn variant was associated with serum triglyceride level (P = 0.026). Interestingly, only subjects that simultaneously exhibit all three polymorphisms showed a significantly elevated BMI (29.30 ± 0.85 vs 26.91 ± 1.19, P = 0.037). Taken together, our data suggest that a combination of polymorphism in the LEP gene 3' flanking region, and Lys109Arg, Lys656Asn variants in LEPR gene is associated with obesity in Chinese Han population.

Relationship Between Leptin G2548A and Leptin Receptor Q223R Gene Polymorphisms and Obesity and Metabolic Syndrome Risk in Tunisian Volunteers

Leptin is a key hormone of weight regulation that modulates food intake. Since the elaboration of the leptin action mechanism, several studies tried to establish the relationship between obesity and the common polymorphisms of leptin (LEP) and leptin receptor (LEPR) genes, but results were controversial. We studied the association of G2548A of the LEP gene and Q223R of LEPR gene polymorphisms with obesity and metabolic syndrome (MetS). We recruited 169 nonobese volunteers (body mass index [BMI] < 30 kg/m(2)) and 160 obese ones (BMI ≥ 30 kg/m(2)). Glucose, insulin, and lipids were measured. BMI, homeostasis model assessment-insulin resistance (HOMA-IR), and daily energy intake were calculated. After adjustment to confounders parameters, 2548AA was found to increase the MetS (p=0.043) and obesity risk (p=0.019) in the studied population. After stratification according to the degree of obesity, the odds ratio [OR] of 2548AA was associated with moderate obesity (p=0.048) and morbid obesity (p=0.048). The LEPR 223RR genotype was associated with obesity in the studied population (OR=1.74, p=0.037) and only in the overweight (OR=1.8, p=0.049). Subjects with 2548AA had significantly higher BMI, daily energy intake, total cholesterol (TC), waist circumference (WC), insulinemia, and low high-density lipoprotein-cholesterol (HDL-C) levels. With regard to 223RR, we noted a significantly higher daily energy intake, BMI, TC, glycemia, insulinemia, HOMA-IR index, and low HDL-C levels. Haplotype model AR (2548A+223R) and AQ (2548A+223Q) increased the risk of obesity (OR=3.36, p<0.001; OR=2.56, p=0.010, respectively). When we added daily energy intake in adjustment, these significant associations disappeared. In addition, the AR and AQ increased the MetS risk. This significant association persisted after we had added daily energy intake in adjustment. This study showed that LEP G2548A and LEPR Q223R polymorphisms and haplotype combination were associated with MetS and obesity risk in Tunisian volunteers.

Using high resolution melting analysis to identify variation of NPY, LEP and IGF-1 genes in Angus cattle

Neuropeptide Y (NPY), leptin (LEP) and insulin-like growth factor 1 (IGF-1) have been proposed as valuable predictors of relative differences among individuals in the regulation of whole-body energy metabolism. The main objective of this study was to assess the allelic frequency of relevant single nucleotide polymorphisms (SNPs) in NPY, LEP and IGF-1 genes using high resolution melting (HRM) analysis. One hundred thirty six female calves from five Aberdeen Angus stud farms were genotyped. An A/G SNP located in intron 2 of the NPY gene (SNPNPY), a C/T SNP located in exon 2 of the LEP gene (SNPLEP), and a T/C SNP located in the promoter region of IGF-1 gene (SNPIGF-1), were the markers genotyped. The favorable allele frequencies in the whole population were 0.23, 0.48 and 0.39 for SNPNPY, SNPLEP and SNPIGF-1, respectively. The average value of FST for the three SNPs in the whole population was 0.015. The analysis of these SNPs indicated a low frequency of favorable alleles and a high homogeneity of the Angus population evaluated. The HRM genotyping described in this report provides a convenient alternative approach to identify SNPs in bovine genes.

Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain

Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding leptin, LEP, and leptin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG. A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, leptin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate. ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p=.068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G-rs10954173G-rs3828942G (p=.035) and AIWG. The rs7799039 G-allele (p=.042) and G-allele of rs3828942 (p=.032) were associated with higher weight gain. Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the leptin-melanocortin pathway.

Study of leptin levels and gene polymorphisms in patients with central precocious puberty

Three single-nucleotide polymorphisms (SNPs) in the leptin (LEP) or leptin receptor (LEPR) genes were assessed for their association with central precocious puberty (CPP). The control group with the A/G SNP at LEPR 223 or A/G SNP at LEPR 109 exhibited significantly higher peak luteinizing hormone (LH) levels. The leptin level in the CPP group was significantly higher than that in the control group, but SNPs in either LEP or LEPR gene could not explain this observation. In conclusion, SNPs at LEPR 223 and LEPR 109 were significantly associated with higher levels of LH in girls without CPP, but none of the genotypes at these SNPs were significantly associated with CPP. The SNP genotypes of LEP (polymorphism at promoter at nt-2548) and LEPR (223A/G, 109A/G) of 219 healthy girls and 249 girls diagnosed with CPP were compared. Allele frequencies in SNPs were compared with anthropometric measures, circulating leptin, hormones (estradiol, follicle-stimulating hormone, and LH), and lipid concentrations for CPP risk.

Translational Approaches for Pharmacotherapy Development for Acute Diarrhea

Areport is presented of a National Institute of Diabetes and Digestive and Kidney Diseases–sponsored single topic conference designed to determine scientific advances needed to encourage development of pharmacotherapy for diarrheal diseases. Acute diarrheal diseases are a global public health problem in developing and developed countries. They are a leading cause of mortality and morbidity for children under the age of 5 worldwide and have a major economic impact in developed countries. Although oral rehydration solution (ORS) along with oral zinc therapy has reduced mortality owing to acute diarrheal diseases, there are essentially no other approved, safe, and effective drugs to decrease stool volume and prevent fluid loss. On September 25–27, 2011, the National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on Translational Approaches for Pharmacotherapy Development for Acute Diarrhea to assess current treatments for acute diarrhea, to identify common host pathways targeted by infectious agents associated with acute diarrhea, to evaluate which pathophysiologic mechanisms are most clinically relevant as potential targets, and to identify promising areas for translational research.

The Effect of Ponderal Index at Birth on the Relationships Between Common LEP and LEPR Polymorphisms and Adiposity in Adolescents

This study examined the effect of ponderal index (PI) at birth on the relationships between eight common polymorphisms of the leptin (LEP) and leptin receptor (LEPR) genes and adiposity in adolescents. A total of 823 European adolescents (45.4% girls) aged 14.8 ± 1.4 years were genotyped for the LEP (rs2167270, rs12706832, rs10244329, rs2071045, and rs3828942) and LEPR (rs1137100, rs1137101, and rs8179183) polymorphisms. The PI was calculated from parental reports of birth weight and length. Fat mass index (FMI) was calculated. Analyses were adjusted for relevant confounders. An "adiposity-risk-allele score" based on genotypes at the three single-nucleotide polymorphisms (SNPs) associated with adolescents' FMI in adolescents within the lower tertile of PI was calculated. The LEP rs10244329 and rs3828942 polymorphisms were associated with higher FMI only in adolescents within the lower PI tertile (+0.55 kg/m(2) per minor T allele, P = 0.040, and +0.58 kg/m(2) per major G allele, P = 0.028, respectively). The LEPR rs8179183 polymorphism was significantly associated with higher FMI in adolescents within the lower PI tertile (+0.87 kg/m(2) per minor C allele, P = 0.006). After correction for multiple comparisons, only the association between the LEPR rs8179183 and FMI persisted. However, each additional risk allele conferred 0.53 kg/m(2) greater FMI in adolescents within the lower tertile of PI (P = 0.008). In conclusion, our results suggest that those adolescents born with lower PI could be more vulnerable to the influence of the LEP rs10244329 and rs3828942 polymorphisms and LEPR rs8179183 polymorphism on total adiposity content. Due to the relatively small sample size, these findings should be replicated in further larger population samples.

Leptin, leptin gene and leptin receptor gene polymorphism in heart failure with preserved ejection fraction

Heart failure with a normal ejection fraction (HFNEF) is common in obesity and coronary artery disease (CAD). Both ischemia and reperfusion induce leptin (LEP) and leptin receptor (LEPR) gene expression. We aimed to investigate the possible associations of serum leptin, leptin gene and leptin receptor gene polymorphism with HFNEF in patients with CAD. 100 Egyptian CAD patients with HFNEF and 100 healthy subjects (the control group) were genotyped for LEP and LEPR polymorphism. Leptin levels were measured. Serum leptin levels were significantly increased in patients compared to the control group. There was a significant increase in the leptin gene (AA genotype) and the leptin receptor gene (RR genotype) in HFNEF patients compared to the control group. Leptin levels, leptin gene (AA genotype) and LEPR (RR genotype) were more associated with NYHA III than with NYHA I and II. We thus concluded that HFNEF is associated with increased serum leptin levels, and the LEP AA genotype or LEPR RR genotype carries at least a threefold increased risk of developing HFNEF.

ZWIĄZEK POLIMORFIZMU GENU LEPTYNY ZE WSKAŹNIKAMI ROZRODU KLACZY RASY POLSKI KOŃ ZIMNOKRWISTY

The objective of the research was to analyze the relationship between leptin genotypes and reproduction indices in cold blood mares. The statistical analysis was conducted on 65 mares from a stud farm in Nowe Jankowice. Based on reproductive outcomes we calculated basic reproduction indices. The leptin polymorphism was determined using the PCR-RFLP method. In the examined population, A and B allele frequencies were identical (0.50). Three genotypic forms of the leptin gene were found to occur: AB, AA, and BB. The most frequently noted form was heterozygotic AB (frequency of 0.47), whereas homozygotic AA and BB occurred with equal frequency of 0.26. The most favourable results for the majority of the other reproduction indices were observed in the AB heterozygotic mare group, whereas the least favourable in the AA mares. The said differences were not statistically significant. No significant effect of the leptin genotype on the reproduction traits in mares was found.

Association Study of BMP4, IL6, Leptin, MMP3, and MTNR1B Gene Promoter Polymorphisms and Adolescent Idiopathic Scoliosis

a genetic association study was performed on 126 patients with adolescent idiopathic scoliosis and 197 healthy controls from independent Hungarian pedigrees. to reveal implication of promoter polymorphisms of bone morphogenetic protein 4 (BMP4), interleukin-6 (IL6), leptin, matrix metalloproteinase-3 (MMP3), melatonin 1B receptor (MTNR1B) genes in adolescent idiopathic scoliosis (AIS). Combinatorial association of these candidate genes was also studied to detect additive effect of certain single-nucleotide polymorphism (SNP) patterns. it was previously unraveled that IL6, MMP3, and MTNR1B genes could be considered as predisposition genes of AIS. Since BMP4 and leptin play a central role in bone formation and remodeling and are in direct interaction with melatonin, IL6, and MMP3, these also can be potential predisposition genes. the genotyping was determined by polymerase chain reaction-restriction fragment length polymorphism. at a single gene level, no significant differences were found for allele and genotype frequencies of the polymorphisms of these genes between cases or controls; therefore, the formerly detected association of IL6, MMP3, and MTNR1B with AIS was not confirmed in the Hungarian population by independent SNP analysis. However, significantly increased AIS risk was observed at particular combinations of genotypes of paired SNPs of the candidate genes. the genetic effect of promoter polymorphisms of BMP4, IL6, leptin, MMP3, and MTNR1B can be synergistic for susceptibility to AIS. The combinatorial effect can modulate the final biological impact of many susceptibility polymorphisms; therefore, this should be considered at the comparison of results from case-control studies of different populations.

Single nucleotide polymorphisms in CAPN and leptin genes associated with meat color and tenderness in Nellore cattle

We analyzed single nucleotide polymorphisms in calpain, leptin, leptin receptor, and growth hormone receptor genes and their association with color, drip and cooking losses of longissimus muscle at 7, 14 and 21 days postmortem in 638 purebred Nellore bulls slaughtered between 22 and 26 months of age. Meat samples were vacuum-packed and aged at 4°C. The single nucleotide polymorphisms T945M, GHR2, E2FB, and CAPN4751 were evaluated. All genotypic classes were observed; however, the T/T genotype of T945M and E2FB was found at a low frequency. A significant association of E2FB with drip loss (a measure of water-holding capacity) was detected at seven days of meat aging. CAPN4751 had an additive effect on red and yellow color intensities. The T allele of CAPN4751 was found to be positively associated with improved meat color, but not with meat tenderness, differing from a previous report indicating that it is associated with meat tenderness. We conclude that the potential for use of CAPN4751 as a marker for these meat quality traits requires further research.

The serum leptin level and body mass index in Melanesian and Micronesian Solomon Islanders: Focus on genetic factors and urbanization

This study examined the association between the serum leptin level and body mass index (BMI) and the effects of urbanization and polymorphisms of leptin (LEP) or leptin receptor (LEPR) genes on the leptin level in three Solomon Islands populations. A Melanesian population living in a remote area (participants: 106 males and 106 females, ages: 18-74 years), a Melanesian population in an urban area (89 and 94, 18-79 years), and a Micronesian population who migrated to a peri-urban area in the 1960s (84 and 69, 18-71 years) were studied. Anthropometric and serum leptin measurements and genotyping for LEP G-2548A and LEPR K109R and Q223R were performed. The prevalence of obesity (BMI ≥ 30 kg/m(2)) was the highest in the Micronesian population (30.1%), followed by the urban (18.6%) and the rural (2.4%) Melanesian population. The serum leptin concentration was the highest in the urban Melanesian, followed by the Micronesian and the rural Melanesian populations (P < 0.05). Interestingly, the parameter coefficients of the leptin concentrations on the BMIs were nearly identical in the urban and rural Melanesians after adjusting for age and gender. The LEPR 223Q/Q genotype was associated with an increased leptin level only in the Micronesian population after adjusting for BMI (P = 0.0008 and 0.0016 referenced to the Q/R and the R/R types, respectively). These observations suggest that the increase in obesity in the Micronesians had a genetic component while that in Melanesians might have been related with the urbanization.

Association analyses of single nucleotide polymorphisms in the LEP and SCD1 genes on the fatty acid profile of muscle fat in Simmental bulls

The aim was to investigate the effect of the genetic polymorphisms of leptin ( LEP) and stearoyl-CoA desaturase ( SCD1) genes on the fatty acid (FA) composition of the muscle of 103 Simmental bulls. Ten single nucleotide polymorphisms (SNP) were detected in exons 2 and 3 of the LEP gene, two of them encoding non-synonymous mutations. Allelic substitution effects of all the SNP on 28 single fatty acids, monounsaturated (MUFA) and polyunsaturated (PUFA) and desaturation indexes were estimated. Both the SCD1 SNP, as well as three SNP of the leptin gene, affected, to different extents, the desaturation of FA into MUFA. Because it was previously proposed that leptin's metabolic action involves down-regulation of SCD1, it is possible that, beyond the mere additive effect of SCD1 gene on FA desaturation, the non-synonymous mutations in the leptin gene also contribute to the variability of FA composition in muscle fat.

Associations between LEP, DGAT1 and FABP4 gene polymorphisms and carcass and meat traits in Nelore and crossbred beef cattle

The aim of this study was to estimate the segregation of leptin ( LEP), diacylglycerol O-acyltransferase ( DGAT1) and fatty acid-binding protein 4 ( FABP4) gene polymorphisms in Nelore ( Bos indicus) and Nelore × Bos taurus beef cattle, and to evaluate their effects on carcass and meat traits. A total of 300 animals were genotyped for the LEP/ BsaAI (Y_11369.1:g.1620G > A), DGAT1-VNTR (18-bp repeat element in the promoter region) and FABP4/ MspA1I (AAFC_01136716.1:g.7516G > C) polymorphisms and phenotyped for rib eye area, backfat thickness (BT), intramuscular fat, shear force, and myofibrillar fragmentation index. The allele substitution effects for each of the polymorphisms on the traits of interest were estimated by regression on the number of copies of a particular allele using the General Linear Model procedure. To keep the experiment wise error rate to the specified level, the Bonferroni adjustment was applied. Although the LEP/ BsaAI polymorphism has shown segregation for association studies in Nelore cattle [f(A) = 0.351], no associations were observed between its alleles and the traits analyzed. The DGAT1-VNTR was found to be polymorphic in Nelore cattle, as well as a potential association with BT. In addition to being non-informative in Nelore animals (allele C was found to be fixed), the FABP4/ MspA1I polymorphism showed no association with the studied traits in crossbred animals.

Association of bovine leptin polymorphisms with energy output and energy storage traits in progeny tested Holstein-Friesian dairy cattle sires

BackgroundLeptin modulates appetite, energy expenditure and the reproductive axis by signalling via its receptor the status of body energy stores to the brain. The present study aimed to quantify the associations between 10 novel and known single nucleotide polymorphisms in genes coding for leptin and leptin receptor with performance traits in 848 Holstein-Friesian sires, estimated from performance of up to 43,117 daughter-parity records per sire.ResultsAll single nucleotide polymorphisms were segregating in this sample population and none deviated (P > 0.05) from Hardy-Weinberg equilibrium. Complete linkage disequilibrium existed between the novel polymorphism LEP-1609, and the previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P < 0.05) with milk protein concentration and calf perinatal mortality. It had a tendency to associate with milk yield (P < 0.1). The G allele of LEP-1238 was associated (P < 0.05) with reduced milk fat concentration, reduced milk protein concentration, longer gestation length and tended to associate (P < 0.1) with an increase in calving difficulty, calf perinatal mortality and somatic cells in the milk. LEP-963 exhibited an association (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and gestation length. It also tended to associate with milk yield (P < 0.1). The R25C SNP associated (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and length of gestation. The T allele of the Y7F SNP significantly associated with reduced angularity (P < 0.01) and reduced milk protein yield (P < 0.05). There was also a tendency (P < 0.1) for Y7F to associate with increased body condition score, reduced milk yield and shorter gestation (P < 0.1). A80V associated with reduced survival in the herd (P < 0.05).ConclusionsSeveral leptin polymorphisms (LEP-2470, LEP-1238, LEP-963, Y7F and R25C) associated with the energetically expensive process of lactogenesis. Only SNP Y7F associated with energy storage. Associations were also observed between leptin polymorphisms and calving difficulty, gestation length and calf perinatal mortality. The lack of an association between the leptin variants investigated with calving interval in this large data set would question the potential importance of these leptin variants, or indeed leptin, in selection for improved fertility in the Holstein-Friesian dairy cow.

Associations between leptin polymorphisms and performance traits in Holstein-Friesian dairy cattle

Associations between leptin polymorphisms and performance traits in Holstein-Friesian dairy cattle

Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival

Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival. The polymorphisms LEP G-2548A and LEPR Q223R were characterized in population-based study consisting of mostly European-American women. The study examined 1,065 women diagnosed with first, primary invasive breast cancer between 1996 and 1997. Controls were 1,108 women frequency matched to the cases by 5-year age group. A modest increase in risk of developing breast cancer was associated with the LEP -2548AA genotype when compared to the LEP -2548GG genotype (age-adjusted OR = 1.30; 95% CI = 1.01-1.66). This association was stronger among postmenopausal women who were obese (OR = 1.86; 95% CI = 0.95-3.64) although the interaction was of borderline statistical significance (P = 0.07). We found no evidence of an association with polymorphisms of either LEP or LEPR in relation to all-cause or breast cancer-specific mortality among women with breast cancer (mean follow-up time = 66.7 months). The effects of these genotypes on breast cancer risk and mortality did not vary significantly when stratified by menopausal status. In summary, our results show that a common variant in LEP may be associated with the risk of developing breast cancer supporting the hypothesis that leptin is involved in breast carcinogenesis.

Bovine gene polymorphisms related to fat deposition and meat tenderness.

Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP), thyroglobulin (TG) and diacylglycerol O-acyltransferase (DGAT1). A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus), Canchim (5/8 Bos taurus + 3/8 Bos indicus), Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus), Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus) and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus) breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM) procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus.

Association of leptin −2548G/A and leptin receptor Q223R polymorphisms with increased risk for oral cancer

We investigated the possible association of DNA polymorphisms -2548G/A and Q223R in the leptin (LEP) and leptin receptor (LEPR) genes, respectively, which both affect the amount of circulating cytokine-type hormone leptin, with risk for development of oral cancer. Polymerase chain reaction-based restriction analysis was performed in DNA samples of 150 patients with oral squamous cell carcinoma (OSCC) and 152 healthy control subjects of equivalent gender, age, and ethnicity (Greeks and Germans). Compared to controls, the homozygous high gene expression genotype A/A of the LEP -2548G/A polymorphism was significantly increased in the subgroups of patients with advanced cancer stages (P = 0.0001; OR 9.0, 95% CI 2.62-30.89), with a positive family history of cancer (P = 0.0346; OR 3.55, 95% CI 1.15-11.01), without tobacco abuse (P = 0.0051; OR 9.69, 95% CI 1.03-91.24), and without alcohol abuse (P = 0.0472; OR 2.16, 95% CI 0.87-5.37). The homozygous low-leptin-binding genotype G/G of the LEPR Q223R polymorphism was strongly associated with an increased risk for OSCC for all patients (P = 0.0028; OR 4.11, 95% CI 1.30-12.97) as well for most of the patient subgroups. The above findings are consistent with the growth-promoting role of leptin in cancer and its induction effect on angiogenesis and metastasis. This is the first study indicating the association of these LEP and LEPR gene polymorphisms with increased risk for OSCC.