The Association Study Between The Polymorphism Of Leptin Receptor Gene, Type 2 Diabetes And Plasma Lipoprotein

Type 2 diabetes mellitus (DM) and obesity are both chronic metabolic barrier disease, and obese patients usually accompanied by dyslipidemia, which are both considered as the risk factors for type 2 diabetes. Recently, along with the development of economic, the improvement of people's living standards and the intensifying of aging population, the incidence of diabetes and obesity are increasing year by year, in which, type 2 DM accounts for about 90 percent to 95 percent. Following the tumor, cardiovascular and cerebrovascular diseases, diabetes has become the most harmful chronic non-communicable diseases to human health. Diabetes diseases can affect many organs and tissues, such as the eyes, kidney, and brains, to cause serious complications, in addition, coupled with its prolonged course and incurable, diabetes threat peoples'health seriously, but also bring heavy burden to the families and society. Now, it is general viewpoint that type 2 diabetes and obesity are multifactorial disease, which mechanism is very complex, including complex interactions among multiple genes, environmental and lifestyle factors. In the same environment incentive effects, the individuals with higher genetic susceptibility are more likely to suffer from type 2 DM, so if the individuals with higher genetic susceptibility can be identified, the incidence can be reduced by improving the lifestyle and taking specific measures. With the development of molecular biology, the research methods in epidemiology has gone deep into micro. Leptin is a protein containing 167 amino acids, the leptin receptor (OB-R, LR) is a large membrane spaning protein that belongs to the gp 130 family of cytokine class I receptors. Besides the neuroendocrine effects of leptin in the control of food intake and energy expenditure, binding of this hormone has been proven in intestine, liver, kidney, skin, stomach, heart, spleen, lung, and so on. At present, the association study between leptin gene, LR gene and their related diseases, such as type 2 diabetes, obesity, and lipid metabolism become a focus of research.Today, the study Conclusions on the association study between leptin gene, LR gene and type 2 DM and obesity are Inconsistent, and also, it is not identified that if there is one or several main effective gene in type 2 DM and obesity. However, studies have found that Gln223Arg polymorphism, which is in the LEPR gene exon6, exists widely in obesity and type 2 DM patients. Our study plans to adopt a case-control study, starting from the SNP, to investigate the allele frequencies of LEPR Gln223Arg gene in Han people live in Chongqing, China, and the association between the polymorphism and type 2 DM and obesity on the basement of PCR-RFLP test.PARTⅠRESEARCH FOR OBESITY AND DYSLIPIDEMIA RELATED WITH TYPE 2 DIABETESObjective: To study the relationship between obesity and type 2 diabetes, as well as dyslipidemia and type 2 diabetes. Methods: The case-control study was applied, comparing 396 objects from 3 hospitals in chonqing of which the case group (diabetic patients) contained 184 patients while 212 were in the control group (non-diabetes), during the period of Oct., 2008 to Feb, 2009. Results all the indexes as body mass index (BMI), waist-hip ratio (WHR), serum total cholesterol (TC) and triglyceride (TG) of the case group were higher than those of the control group. And the t-test demonstrated these differences are statistically significant; the overweight and obesity rates(64.67%), the detection rates of high cholesterol(27.17%) and high triglyceride(50.00%) of the case group were higher than the control group, and the chi-square test showed statistically significant differences; The multi-factor non-conditional Logistic regression analysis showed that hypercholesterolemia, hypertriglyceride, overweight and obesity are major risk factors for diabetes. Conclusion Obesity and dyslipidemia are related to the occurrence of type 2 diabetes. Controlling weight and a reasonable diet are important measures to prevent type 2 diabetes.PARTⅡTHE CASE-CONTROL RESEACH FOR LEPTIN RECEPTOR GENE GIn223Arg POLYMORPHISM AND TYPE 2 DIABETES MELLITUSObjective: To study the possible relationship between the polymorphism of leptin receptor (LEPR) gene Gln223Arg and type 2 diabetes. Methods A case-control study was adopted to investigate 336 patients of two hospitals in Chongqing (the Jiulongpo first people's hospital and the Chonggang general hospital), including patients on the first visit to diabetes outpatient and inpatient departments, patients with other diseases, and patients coming for the physical examination, then 172 patients were assigned into the case group (with diabetes) and 164 into the control group (without diabetes). Then we investigate their risk factors of diabetes, and meanwhile test the polymorphism of leptin receptor (LEPR) gene Gln223Arg by the polymerase chain reaction—restriction fragment length polymorphism (PCR - RFLP), to analyze its relationship with type 2 diabetes. Results The genotype frequency distribution of AA, GA, GG in this crowd were 0.015, 0307 and 0.678, the allele frequency of A and G were respectively 0.202 and 0.798, genotype frequency distribution accorded with H—W balance (x2 = 3.081, P = 0.079). The detection rate (74.42%) of genotype GG in the case group was higher than that in the control group (60.98%), while the detection rate (25.28%) of genotype AA and GA was lower than the control group (39.02%), differences were statistically significant (P = 0.008); results of the single factor analysis indicated that the hypercholeslerolemia, hypertriglyceridemia, low level of high-density lipoprotein and the polymorphism of Gln223Arg gene were the risk factors for type 2 diabetes (P <0.05); Unconditional Logistic regression analysis revealed that high level of total cholesterol (TC), low level of high-density lipoprotein (HDL-C), high level of waist-hip ratio (WHR), the diabetes family history and the mutation of LEPR gene Gln223Arg were risk factors for the incidence of type 2 diabetes.Conclusion Polymorphism of leptin receptor (LEPR) gene Gln223Arg was probably relevant to type 2 diabetes.PARTⅢTHE RELATIONSHIP BETWEEN LEPTIN RECEPTOR GENE GIn223Arg POLYMORPHISM AND OBESITYMethods A total of 336 outpatients and first visit inpatients of two hospitals (the Chongqing Jiulongpo First People's Hospital and the Chonggang Hospital) in Chongqing city. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was adapted to test the polymorphism of leptin receptor gene Gln223Arg, and we analyzed its relationship with systemic obesity and abdominal obesity.Results The genotype distribution frequency of AA, GA, GG in this crowd were 0.015, 0.307 and 0.678, the allelic variation frequency of allele A and G were 0.202 and 0.798. The genotype distribution frequency accorded with the H-W balance (x2= 3.081,P =0.079).According to the chi-square test, there was no significant difference statistically of the genotype and allelic variation frequency between systemic obesity group and none obesity group,as well as between abdominal obesity group and its control group.The Logistic regression revealed that high triglycerides (TG) is a risk factor to systemic obesity, while there was no significant difference statistically of the LR gene Gln223Arg's variation frequency between these two groups. Although the stratified chi-square test to type 2 DM indicated that, among patients with type 2 diabetes, both the difference of the gene type and allelic variation frequency between systemic obesity group and none obesity group were statistically significant (P<0.05); the difference of the gene type and allelic variation frequency between abdominal obesity group and control group were not statistically significant (P>0.05);the stratified logistic regression revealed that there were no relationship between Gln223Arg and overweight-obese both among the diabetic group and non-diabetic group.Conclusions There was no relationship between the polymorphism of leptin receptor gene Gln223Arg and overweight-obesity.