BACKGROUND: This 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.
METHODS: Convenience 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).
RESULTS: The 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.
CONCLUSIONS: The 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.
BACKGROUND: Leptin (LEP) G-2548A (rs7799039), leptin receptor (LEPR) Q223R (rs1137101) and tumor necrosis factor (TNF)-α G-308A (rs1800629) gene variants have been reported to be associated with obesity, although results for subjects from different countries have been controversial. The aim of this study was to determine the prevalence of overweight and obesity in Malaysian adolescents and the association of these polymorphisms with overweight and obese or over-fat adolescents.
METHODS: A total of 613 adolescents (241 Malay, 219 Chinese, 153 Indian) were enrolled. Anthropometric measurements of body mass index (BMI) and body fat percentage were used to classify subjects as controls (non-overweight/obese or normal fat) or as cases (overweight/obese or over-fat). Genomic DNA was extracted from oral buccal mucosa cells for genotyping using polymerase chain reaction-restriction fragment length polymorphism and data obtained were statistically analyzed.
RESULTS: A total of 23.3% of subjects were overweight/obese whereas 11.4% were over-fat; there were significantly more overweight/obese and over-fat Indian and Malay adolescents compared to Chinese (P < 0.001). A allele was the minor one for LEPR Q223R and TNF-α G-308A in all ethnic groups, whereas G allele was minor for LEP G-2548A in Chinese and Malay adolescents, except for Indian adolescents. Indian male adolescents with AA genotype for LEP G-2548A were associated with overweight/obesity (P = 0.025; odds ratio, 3.64; 95% confidence interval: 1.15-11.54). Despite the lack of association observed for LEPR Q223R and TNF-α G-308A, Indian and Chinese subjects with AA risk genotype for LEPR Q223R/LEP G-2548A and TNF-α G-308A/LEP G-2548A, respectively, had increased mean BMI (P = 0.049, P = 0.016).
CONCLUSIONS: Genotype distribution and association of these polymorphisms with overweight/obesity vary between ethnic groups and genders. Nevertheless, the LEP G-2548A risk allele may be associated with overweight/obese Indian male adolescents in Malaysia.
KEYWORDS: adolescents; body fat percentage; body mass index; leptin; leptin receptor; single nucleotide polymorphism; tumor necrosis factor-α
Leptin is known as the adipose peptide hormone. It plays an important role in the regulation of body fat and inhibits food intake by its action. Moreover, it is believed that leptin level deductions might be the cause of obesity and may play an important role in the development of Type 2 Diabetes Mellitus (T2DM), as well as in cardiovascular diseases (CVD). The Leptin Receptor (LEPR) gene and its polymorphisms have not been extensively studied in relation to the T2DM and its complications in various populations. In this study, we have determined the association of Gln223Agr loci of LEPR gene in three ethnic groups of Malaysia, namely: Malays, Chinese and Indians. A total of 284 T2DM subjects and 281 healthy individuals were recruited based on International Diabetes Federation (IDF) criteria. Genomic DNA was extracted from the buccal specimens of the subjects. The commercial polymerase chain reaction (PCR) method was carried out by proper restriction enzyme MSP I to both amplify and digest the Gln223Agr polymorphism. The p-value among the three studied races was 0.057, 0.011 and 0.095, respectively. The values such as age, WHR, FPG, HbA1C, LDL, HDL, Chol and Family History were significantly different among the subjects with Gln223Agr polymorphism of LEPR (p < 0.05).
Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD.
The occurrence of metabolic syndrome (MS) in schizophrenia patients receiving long-term antipsychotics (APs) contributes to their high mortality rate. We aimed to determine whether genetic polymorphisms of identified candidate genes are associated with MS in our study population.
Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.