LEP G2548A Research Articles

LEP G2548A polymorphism is associated with increased serum leptin and insulin resistance among T2DM Malaysian patients.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome that is rapidly increasing across the world, especially in Malaysia. Leptin plays a vital role in the regulation of metabolism through its effect on peripheral tissues. G2548A polymorphism in the LEP gene promoter has been associated with insulin resistance, leptin, and type 2 diabetes mellitus across different population, but has not been inclusively reported within the Malaysian population. Thus, our study aimed to investigate the impact of G2548A polymorphism on serum leptin levels and insulin resistance among Malaysian T2DM patients. This case-control study involved 150 T2DM patients and 150 non-diabetic volunteers from ethnic Malays, Chinese and Indians. Genotyping of G2548A polymorphism was carried out using PCR-RFLP. Serum leptin and insulin levels were determined via ELISA. ANOVA and Chi-square tests were used to determine the distribution of genotypes and allelic frequencies based on serum leptin and insulin levels. Frequency of AA genotype and A allele of G2548A variant were significantly (P < 0.05) higher in T2DM patients of Malay and Indian ethnicities (4%, 35%, and 36%, 57%, respectively) as compared to the control groups (0%, 22%, and 18%, 35%, respectively). Fasting serum leptin levels were significantly (P < 0.001) higher in T2DM patients compared to non-diabetic subjects (166.78 pg/ml, 101.94 pg/ml, respectively). Additionally, elevated serum leptin, insulin levels, and BMI in diabetic patients were found to be associated with the AA genotype of this variant, compared to GG, and GA genotypes (P < 0.05). Our findings suggest a significant association between G2548A polymorphism among Malaysian T2DM subjects, particularly among Malay and Indian ethnic groups. Moreover, the A allele frequency of the G2548A variant significantly increased the risk of T2DM and is significantly associated with increased serum leptin, insulin levels, and elevated BMI.

Association of LEP G2548A and LEPR Gln223Arg Gene Polymorphism with Unexplained Infertility in North Indian Population

Association of LEP G2548A and LEPR Gln223Arg Gene Polymorphism with Unexplained Infertility in North Indian Population

Leptin gene (Lep) G-2548A polymorphism in patients with and without osteoporosis

Leptin plays several important roles in the body, such as body mass control and bone remodeling. Previous research suggests that LEP G-2548A gene polymorphism may be associated with increased risk of osteoporosis. This study aimed at analyzing LEP G-2548A polymorphism in Indonesian patients with and without osteoporosis. DNA samples were collected from 50 subjects with osteoporosis and 50 subjects without osteoporosis. The DNA fragments were amplified with LEP G-2548A primers using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis using the HHAI restriction enzyme. The distribution of the genotypes and alleles in the test and control groups were determined and were compared. The frequency of the AA genotype of LEP G-2548A was higher in the osteoporosis group than in the control group. However, the differences in genotype and allele frequencies between the two groups were not statistically significant (p > 0.05). The genotypes and alleles of LEP G-2548A gene polymorphism did not differ significantly between Indonesian patients with and without osteoporosis.

Effect of selected polymorphisms of genes lep, MTHFR and FTO to BMI level and gender-specificity

The aim of this study is to investigate the effect of selected polymorphisms LEP (G2548A), MTHFR (C677T) and FTO (rs1121980) on body mass index in humans. In the study participated 79 people from Slovakia with some genetic relatedness. Genomic DNA was isolated from the buccal swabs using a commercial kit Qiagen DNA Mini Kit (Qiagen). The detection of SNP polymorphisms in human genes LEP, MTHFR and FTO was performed using molecular genetics methods such as PCR-RFLP and ARMS. The most common genotypes in all 3 polymorphism were found in heterozygous form (for LEP AG = 0.5190, for MTHFR CT = 0.519, for FTO CT =0.4051). The LEP gene had increased frequency of G allele (0.5506), the MTHFR gene T allele (0.6646) and FTO gene T allele (0.50635). The least frequent genotype in LEP was AA (0.1899), in MTHFR was TT (0.0759), in FTO it was CC (0.2911). According to the results we can assume that the genotypes AA (LEP G2548A), CC (FTO rs1121980) and TT (MTHFR C677T) in case of women have a protective effect on the prevalence of obesity, based on BMI, compared to the other genotypes and this polymorphism is gender-specific. Added anthropometric measurements, blood test and extension of the group in the future evaluation could increase the statistical relevance in relation to obesity and gender-specificity.

Effect modification by region in the associations of LEP G2548A and LEPR Q223R polymorphisms with statin-induced CK elevation.

We investigated the associations of LEP G2548A and LEPR Q223R polymorphisms with statin-induced creatine kinase (CK) elevation among Chinese patients with hyperlipidemia. A total of587 enrolled individuals were treated with 20 mg/d oral simvastatin for 8 consecutive weeks. Genotyping of LEP G2548A and LEPR Q223R were conducted using PCR-RFLP. Multiple regression analyses showed that, in the Dongzhi region only, patients carrying the LEP AA genotype had a significantly greater increase in CK levels compared to those carrying the AG+GG genotypes after four weeks (P = 0.004) and eight weeks (P < 0.001) consecutive simvastatin treatment. Patients were further divided into three groups based on the tertiles of the CK distribution. Compared to subjects in the lowest tertile of CK elevation, the adjusted relative odds of having the AG+GG genotypes among subjects in the highest tertile was 0.5 (95% CI, 0.3 to 0.7) and 0.4 (95% CI, 0.2 to 0.6) after the fourth and eighth weeks, respectively. The interaction terms between the Beijing or Dongzhi region and the LEP GA+AA genotypes were marginally significant for CK elevation at the fourth week (P = 0.057) and significant for CK elevation at the eighth week (P = 0.002). The adverse effect of the LEP G2548A polymorphism on increasing CK levels may be dependent on the environmental milieu. It suggests that lifestyle interventions might offset the side effects of simvastatin therapy among those with genetic susceptibility. Further research is needed to identify specific individual-level factors for clinical practice that modify the effect of genotype.

Polymorphisms in Lep and Lepr Genes in Infants: Correlation with Serum Leptin Values in the First 6 Months of Life

ABSTRACTObjective: Because several studies indicate that polymorphisms in leptin (Lep) and leptin receptor (Lepr) genes play a central role in determining obesity, we analyzed 2 single nucleotide polymorphisms (SNPs) in the Lep gene (Lep G2548A and A19G) and one in the Lepr gene (Lepr A668G) to verify the effect of the 3 SNPs on leptin concentrations in infancy.Methods: We enrolled 80 healthy Caucasian infants under 6 months of age, who were genotyped for the 3 SNPs with amplification refractory mutation system–mismatch amplification mutation assay (ARMS-MAMA) real-time polymerase chain reaction (PCR). Serum leptin values were measured with a radioimmunoassay method. Statistical significance was set at p < 0.05.Results: There were no significant differences between individually analyzed leptin polymorphisms Lep G2548A and A19G and serum leptin levels (p > 0.05). Because we found that Lep G2548A and A19G are in linkage disequilibrium on chromosome 7, we performed the haplotype analysis for Lep G2548A and Lep A19G. We obtained higher serum leptin levels in infants with the GG/GG haplotype (p < 0.05). Regarding receptor, we found higher leptin levels in GG-genotype infants for Lepr A668G (p < 0.001). Considering the 3 SNPs together, we found higher serum leptin values in GG/GG-GG infants (LepG2548A/A19G-Lepr A668G; p < 0.001).Conclusion: We obtained higher serum leptin levels in infants with the GG genotype for Lepr A668G, with haplotype GG/GG for Lep G2548A/A19G, and with GG/GG-GG (LepG2548A/A19G-Lepr A668G); thus, it seems that the genotype GG could be a protector against obesity development in infancy and adulthood. Moreover, these data confirm that not variations in the Lep gene as well as in the Lepr gene could play a role in weight gain. Further studies are needed to evaluate the role of genetics and the environment in a predisposition toward obesity later in life.

Associations between LEP G2548A polymorphisms and lipids metabolism

The aim of this study was to determine the population structure based on identification of G2548A polymorphism in leptin gene and analyse its impact on selected traits related with lipids metabolism as well as obesity. Totally, 236 human samples were included in SNP genotyping using PCR-RFLP method and endonuclease Hha I. The impact of locus was assessed for biochemical parameters: BMI, level of total, HDL and LDL cholesterol. In population the prevalence of A allele was detected. The highest proportion was found for heterozygous individuals (0.44). The observed heterozygosity indicated relative sufficient proportion of heterozygotes but the F IS index showed positive value (0.1) that can signalize the increase of homozygotes proportion. The association analysis using GLM procedure proved significant impact of LEP genotypes on each of selected parameter. The results showed the significant role of leptin in human nutritional status and confirmed its value as candidate gene of lipids metabolism disorders.

Leptin promoter variant G2548A is associated with serum leptin and HDL-C levels in a case control observational study in association with obesity in a Pakistani cohort.

Leptin is a protein hormone synthesized by adipocytes and is involved in the regulation of food intake and energy expenditure. We hypothesized that any change in the promoter sequence can affect the expression of the gene and hence leptin protein levels in the serum. The aim of the current study was to investigate the relationship of such a promoter variant of the leptin gene, G-2548A polymorphism, with obesity and its effect on various anthropometric and metabolic parameters in a Pakistani cohort consisting of 250 obese and 225 non-obese control subjects. Body weight, height, waist circumference (WC), hip circumference (HC) and blood pressure (BP) were measured by standard methods and levels of fasting blood glucose (FBG), total cholesterol, triglycerides, HDLC, LDLC, and leptin were determined. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the LEP G-2548A polymorphism showed significant association with obesity in Pakistan. In addition, the polymorphism showed association with weight, height, BMI, WC, HDLC and serum leptin levels. The findings suggest that the leptin promoter G-2548A variant may play its part in the progression to obesity by not only affecting the body's fat distribution but also by changing the serum leptin and HDLC levels.

Effects of LEP G2548A and LEPR Q223R Polymorphisms on Serum Lipids and Response to Simvastatin Treatment in Chinese Patients With Primary Hyperlipidemia.

To investigate whether LEP G2548A and LEPR Q223R polymorphisms influence serum lipid levels and whether the 2 polymorphisms affect the efficacy of simvastatin treatment in Chinese patients with primary hyperlipidemia. We used an extreme sampling approach by selecting 212 individuals from the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n = 106 in each group of good or bad response) from a total of 734 samples with primary hyperlipidemia. They were treated with simvastatin orally 20 mg/d. Fasting serum lipids were measured at baseline and after 4 and 8 weeks of treatment. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism. More patients in the good response group (27%) had LEPR Q223R than in the bad response group (16%, P = .046). Secondary stratified analyses showed that patients carrying the RR genotype of the LEPR Q223R gene had significantly higher high-density lipoprotein cholesterol levels than those with the QR genotype at baseline ( P = .034) among good responders. After 29 consecutive days of treatment with simvastatin, patients carrying the RR genotype had a significantly larger decrease in triglycerides (change: -0.74 ± 0.92, P = .036) and total cholesterol levels (change: -1.77 ± 0.68, P = .023) compared with those carrying QR genotype among bad responders. After Bonferroni correction, the results were not statistically significant. LEPR Q223R polymorphism, but not LEP G2548A, could modulate the efficacy of simvastatin in Chinese patients with primary hyperlipidemia.

Association between Leptin G2548A and Leptin Receptor Q223R Polymorphisms with Type 2 Diabetes in an Iranian Population.

The leptin (LEP G2548A) and leptin receptor (LEPR Q223R) gene polymorphisms have been variably associated with type 2 diabetes (T2D) in different populations. In this study we hypothesized that these variants might be associated with T2D and related metabolic traits in an Iranian population. The LEP G2548A and LEPR Q223R genotypes were determined by PCR-RFLP in 378 normoglycemic controls and 154 T2D patients. Bonferroni correction was applied for the correction of multiple testing. The A allele of the LEP G2548A polymorphism was more prevalent in females of the T2D group than the controls (p = 0.009). In a recessive model (GG+GA vs. AA), the frequency of the AA genotype was higher in female patients compared to normoglycemic subjects 134.9% vs. 19.3%, OR 2.60 (1.27-5.31), p = 0.0091. Multivariate logistic regression analysis also showed that the AA genotype of the LEP G2548A polymorphism is an independent risk factor for T2D in females. No significant association was found between the allele and genotype frequencies of the LEPR Q223R variant with T2D in female and male groups. In addition, no significant difference in anthropometrical and biochemical parameters was observed between the genotypes of LEP and LEPR variants in gender-specific groups in both non-diabetic and diabetic subjects. Our results suggest that the LEP G2548A polymorphisms might associate with T2D among Iranian female subjects, whereas the LEPR Q223R variant is not associated with T2D and its related metabolic traits in this population.

The Association of Polymorphisms in Leptin/Leptin Receptor Genes and Ghrelin/Ghrelin Receptor Genes With Overweight/Obesity and the Related Metabolic Disturbances: A Review.

Context:Leptin and ghrelin are two important appetite and energy balance-regulating peptides. Common polymorphisms in the genes coding these peptides and their related receptors are shown to be associated with body weight, different markers of obesity and metabolic abnormalities. This review article aims to investigate the association of common polymorphisms of these genes with overweight/obesity and the metabolic disturbances related to it.Evidence Acquisition:The keywords leptin, ghrelin, polymorphism, single-nucleotide polymorphism (SNP), obesity, overweight, Body Mass Index, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (MeSH headings) were used to search in the following databases: Pubmed, Sciencedirect (Elsevier), and Google scholar. Overall, 24 case-control studies, relevant to our topic, met the criteria and were included in the review.Results:The most prevalent leptin/leptin receptor genes (LEP/LEPR) and ghrelin/ghrelin receptor genes (GHRL/GHSR) single nucleotide polymorphisms studied were LEP G-2548A, LEPR Q223R, and Leu72Met, respectively. Nine studies of the 17 studies on LEP/LEPR, and three studies of the seven studies on GHRL/GHSR showed significant relationships.Conclusions:In general, our study suggests that the association between LEP/LEPR and GHRL/GHSR with overweight/obesity and the related metabolic disturbances is inconclusive. These results may be due to unidentified gene-environment interactions. More investigations are needed to further clarify this association.

Role of leptin G-2548A polymorphism in age- and gender-specific development of obesity.

Leptin is involved in the regulation of food intake and energy expenditure, and therefore, is central to adipositysensing pathway. We examined the relationship of the leptin G-2548A polymorphism with obesity and obesityrelated anthropometric and metabolic parameters in a total of 394 (239 obese and 155 non-obese) subjects between 5 and 45 years of age. Body weight, height, waist circumference (WC), hip circumference (HC) and blood pressure (BP) were measured. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Levels of fasting blood glucose (FBG), insulin, leptin and leptin receptor were determined, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The LEP G-2548A polymorphism showed association with obesity in children and adolescents (less than or equal to 18 years of age) but not in adults. However, analysis by gender stratification revealed association with obesity in girls only. In addition, G-2548A polymorphism showed association with BMI, WC, HC, fasting blood glucose and serum leptin levels. This suggests that G-2548A polymorphism may influence the susceptibility to metabolic disturbances and obesity at an early life. Further investigation with a larger sample size is required to validate the effect of LEP G-2548A polymorphism in obese Pakistani girls.

A study on oncogenic role of leptin and leptin receptor in oral squamous cell.

Leptin been mainly produced by adipose tissue and cancer cells is the most studied adipokine, amongst the several cytokines. Leptin is an antiapoptotic molecule and inducer of cancer stem cells as well as activates cell proliferation. Its oncogenic, mitogenic, proinflammatory and proangiogenic actions lead to its vital roles in tumourigenesis. Two common functional DNA polymorphisms in the genes of leptin G2548A (LEP) and leptin receptor A668G (LEPR) affect the amount of circulating cytokine-type hormone leptin with risk for development of oral squamous cell carcinoma (OSCC). The present study investigated whether these LEP and LEPR gene polymorphisms are affecting risk for OSCC by comparing the genotypes of patients with controls. A total of 306 OSCC and 228 controls participated in this study. We have determined the frequency of LEP (G2548A) and LEPR (A668G) gene polymorphisms in OSCC cases and controls by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The incidence of leptin gene G2548A homozygous mutant AA polymorphism was significantly increased in the OSCC patients (p = 0.002, odds ratio (OR) = 2.4, 95 % confidence interval (CI) = 1.37-4.22) when compared with controls, and leptin receptor A668G homozygous mutant GG polymorphism was significantly high in the OSCC patients as compared to controls (p = 0.000, OR = 3.8, 95 % CI = 1.98-7.62). The polymorphism of homozygous mutant allele A of leptin gene and G allele of leptin receptor may be associated with increased risk for OSCC. The observations showed regular increase of supporting role of leptin in OSCC. The present study showed an association of AA genotype and A allele of LEP G2548A as well as GG genotype and G allele of LEPR A668G polymorphisms with increased risk for OSCC in north Indian patients. Moreover, the combination of both the polymorphisms may be involved in susceptibility and progression of OSCC.

The LEP G-2548A gene polymorphism is associated with age at menarche and breast cancer susceptibility

Leptin is an adipocytokine made by fat cells and plays a key role in proliferation, cell survival, migration and immune response. It has a powerful effect on the initiation of puberty and in determining age at menarche. The current study is the first investigation to examine the effect of G-2548A leptin gene polymorphism on the age at menarche and breast cancer susceptibility. This case–control study was performed on 203 patients with breast cancer and 171 healthy women. The leptin genotypes were determined using the PCR-RFLP method and age at menarche was obtained by questionnaires. There was a significant difference between the leptin G-2548A genotypes between case and control groups (P<0.05). AA genotype is significantly higher in patients compared to the controls. Furthermore, women carrying the AA genotype had a significantly younger age at menarche (12.47years) than women with the AG (12.94years) and GG (13.47years) genotypes. Also, we found that the AA genotype frequency in women with age at menarche <13years was higher than in women with age at menarche ≥13years (OR: 3.4, 95% CI: 1.7–6.7, P: 0.001). In conclusion, the G-2548A leptin gene polymorphism has an important role in the onset of menarche and breast cancer susceptibility.

Association of leptin gene polymorphism G-2548A with metabolic and anthropometric parameters in obese patients in a Serbian population: pilot study

Aim: The aim of this pilot study was to investigate possible associations of LEP promoter polymorphism LEP G-2548A and obesity-associated metabolic and antropometric parameters in obese population. Materials & methods: Group of 31 patients with hyperalimentary type of obesity (mean age: 39.26 ± 11.45 years; BMI: 41.51 ± 9.22 kg/m2) and 36 healthy, nonobese, normal weight subjects (mean age: 33.55 ± 6.46 years; BMI: 22.63 ± 1.94 kg/m2) were studied. Blood samples were collected for DNA isolation, serum leptin and serum lipids measurements. LEP G-2548A genotypes were determined by PCR restriction fragment length polymorphism based analyses. Results: No significant differences in genotype and allele frequencies of the LEP G-2548A polymorphism were detected between obese and normal weight subjects. No association was found between this polymorphism and BMI. Obese subjects had statistically significant increase in serum leptin levels compared with control, while no association between leptin concentration and LEP polymorphism LEP G-2548A was found. There is a statistically significant association of LEP G-2548A genotypes with LDL (p < 0.05), LDL/HDL ratio (p < 0.001), apoB (p < 0.01), body weight (p < 0.001) and waist circumference (p < 0.001). Conclusion: Our findings indicate that there is an association between LEP G-2548A polymorphism and metabolic and anthropometric parameters in obese patients in a Serbian population.

Leptin and leptin receptor gene polymorphisms and their association with plasma leptin levels and obesity in a multi-ethnic Malaysian suburban population.

BackgroundThis study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) in leptin gene LEP (A19G and G2548A) and leptin receptor gene LEPR (K109R and Q223R) and their association with fasting plasma leptin level (PLL) and obesity in a Malaysian suburban population in Kampar, Perak.MethodsConvenience sampling was performed with informed consents, and the study sample was drawn from patients who were patrons of the Kampar Health Clinic. A total of 408 subjects (mean age, 52.4 ± 13.7 years; 169 men, 239 women; 190 obese, 218 non-obese; 148 Malays, 177 ethnic Chinese, 83 ethnic Indians) participated. Socio-demographic data and anthropometric measurements were taken, and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsThe LEP A19G, G2548A and LEPR K109R, Q223R variant allele frequencies were 0.74, 0.67 and 0.61, 0.79, respectively. The genotype and allele distributions of these gene variants were significantly different among ethnic groups, but not among body mass index (BMI) classes. Subjects with LEPR K109 and Q223 allele had significantly higher systolic blood pressure and adiposity indices after adjustment for ethnicity (higher BMI, total body and subcutaneous fat; lower skeletal muscle percentage). Subjects with LEPR 109R allele had lower PLL than their wild-type allele counterparts. The influence of LEP A19G and G2548A SNPs on blood pressures, anthropometrics, and PLL was not evident. Interestingly, synergistic effect of the LEP and LEPR SNPs was observed as subjects homozygous for all four SNPs studied exhibited significantly higher subcutaneous fat and PLL than those with other genotype combinations.ConclusionsThe LEP and LEPR SNPs in this study may not be an obesity marker among Malaysians in this population, but were associated with ethnicity. Our findings suggest that each of these SNPs contributes to minor but significant variation in obesity-related traits and in combination they display synergistic effects on subcutaneous fat and PLL.

Measurement of the levels of leptin, BDNF associated with polymorphisms LEP G2548A, LEPR Gln223Arg and BDNF Val66Met in Thai with metabolic syndrome

BackgroundMetabolic syndrome is a cluster of metabolic risk factors including dyslipidemia, impaired glucose tolerance, hypertension and central obesity. BDNF (Brain-derived neurotrophic factor) and leptin have been implied in the energy homeostasis. The purposes of this study were to examine concentrations of leptin, BDNF and biochemical parameters in metabolic-syndrome subjects and healthy controls, and also to search for associations of leptin gene (LEP) G2548A, leptin receptor gene (LEPR) Gln223Arg, and BDNF gene (BDNF) Val66Met polymorphisms with leptin levels, BDNF levels and metabolic syndrome among Thais.MethodsThe case-controlled design was performed using 322 Thai volunteers (160 metabolic-syndrome subjects; 162 controls) during the health screening program. Metabolic syndrome was assessed by using the modified National Cholesterol Education Program, Adult Treatment Panel III criteria. The levels of leptin, BDNF, insulin, glucose and lipids were measured in samples. Genotyping of LEP G2548A, LEPR Gln223Arg and BDNF Val66Met was carried out using polymerase chain reaction-restriction fragment length polymorphism technique.ResultsSerum leptin levels were significantly higher in the metabolic-syndrome group than the control group (p < 0.01), but the BDNF difference between them was not significant. Significant associations of LEPR Gln223Arg polymorphism were found with leptin and glucose levels (p < 0.05), after adjusting for potential covariates. This LEPR polymorphism in the metabolic-syndrome group was also significantly more frequent than in the control group (p < 0.05). However, other gene polymorphisms, LEP G2548A and BDNF Val66Met, showed no significant relationship with leptin levels, BDNF levels or metabolic syndrome.ConclusionThese findings suggest leptin levels are linked with metabolic syndrome. LEPR Gln223Arg polymorphism impacted leptin concentrations, and this gene polymorphism may influence susceptibility to metabolic syndrome among Thais.

Leptin gene G-2548A polymorphism in Iranian subjects with metabolic syndrome.

Metabolic syndrome (MetS) is a serious public health problem and one of the important risk factors contributing to cardiovascular disease in developed countries. Adipose tissue is considered a secretory organ that releases a variety of molecules referred to adipocytokines such as leptin, so polymorphism of these protein genes may play an important role in development of MetS. Therefore, the aim of this study was to determine the genetic varieties of Lep-2548G/A between MetS and healthy subjects. In this case-control study, the relationship between LEP G-2548A polymorphism and MetS was evaluated in Iranian participants, 200 patients (142 women and 58 men) and 200 controls (122 women and 78 men) who were randomly selected from Hamadan city. Blood samples were collected; moreover, routine biochemical analysis, DNA extraction, and serum leptin measurements were done. LEP G-2548A genotypes were identified by a PCR-RFLP technique. Our findings showed significant differences between biochemical factors and leptin concentration between two groups. Females show more serum leptin concentration than males. There was no significant difference in polymorphism of Lep-2548G/A between MetS and healthy subjects. Although we cannot find any correlation between leptin concentration and BMI, some relation exists with LDL-C, HDL-C and TG (p < 0.05). In summary, it is concluded that leptin probably has a key role in metabolic syndrome development and further research in this area is needed.

Association of LEP G2548A and LEPR Q223R Polymorphisms with Cancer Susceptibility: Evidence from a Meta-Analysis

BackgroundNumerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations.MethodsWe searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities.ResultsThe final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity.ConclusionsDespite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.

The LEP G-2548A Polymorphism is not Associated with Breast Cancer Susceptibility in Obese Western Mexican Women

Breast cancer incidence and the prevalence of obesity have considerably increased in Mexican women. The LEP G-2548A polymorphism has been associated with obesity and breast cancer risk in several ethnic populations. We hypothesize that G-2548A LEP polymorphism could be associated with breast cancer risk in women Mexican population. A total of 319 women were included in this study, 130 breast cancer patients and 189 control women. The data collected included anthropometric measurements and menopausal status, and a blood sample was obtained to evaluate SNPs using a PCR-RFLP analysis. No statistically significant associations were identified between breast cancer risk and the LEP G-2548A polymorphism in obese or normal-weight subgroups regardless of menopausal status. Our findings suggest that the LEP G-2548A polymorphism is not associated with breast cancer risk in obese western Mexican women. Our results indicate that, for western Mexican women, the LEP G-2548A polymorphism does not affect breast cancer susceptibility in obese or normal-weight subgroups regardless of menopausal status.