| With the rapid increase in the prevalence of obesity all over the world, obesity has become a serious health problem. Obesity is frequently associated with the development of type 2 diabetes, hypertension, hyperlipidaemia and coronary heart disease. And the mortality in obese people is higher than non-obese people. So the prevention and therapy of obesity becomes a main task in medical field. Although obesity has been shown to have a complex etiology, it is clear that a genetic predisposition to this disease is very important. A recent study suggests that as much as 50-70% of variation in body mass index(BMI) is attributable to genetic difference. Otherwise, body fat distribution, hypertension and the metabolism of glucose and lipid are also used as additional phenotypes . Recently, several genes predisposed to obesity have become the candidate genes for studies on obesity. So it should be of interests to study the relationship between the variants of candidate genes and phenotypes in obese people. The present study was to investigate the association of variants in leptin receptor (LepRb), leptin and peroxisome proliferators-actived receptor(-2 (PPAR(-2) genes with obesity and metabolic abnormalities in Chinese obese population.The genotypes of variants in exon 4,9-10,11,13-14,20 of LepRb gene were determined by PCR-SSCP assay and that of the variant in exon 6 of LepRb gene was determined by PCR-RFLP assay in 232 unrelated subjects of Chinese population ( including 130 simple obese people and 102 non-obese people). The clinical data were also analyzed. Results: 1)With SSCP , RFLP and direct DNA sequencing, five missense(Lys109Arg, Gln223Arg, Lys656Asn Ala976Asp, Ser1075Ala) point mutations, one nonsense (Pro1019Pro) point mutation and one deletion (AGA/(GA, nt=1032) point mutation were identified, and the missense (Ser1075Ala) and absent (AGA/(GA, nt=1032) point mutation were two novel ones since no such kind of mutations were reported up to now in obese subjects. 2) No significant difference of genotype frequency of Lys109Arg, Gln223Arg, Lys656Asn variants in LepR gene was observed between obese and n0n-obese group. 3) In obese group, "G" Allele of Gln223Arg variant was associated with increased BMI (33.04(3.36 vs 30.12(3.43, P=0.036); "G" Allele of Lys656Asn variant was associated with increased triglyceride (1.74(0.91 vs 0.95(0.32, P=0.013); and "G" Allele of Lys109Arg variant was associated with increased systolic blood pressure ( 131.25(8.54 vs105.02(7.07, P=0.021) and increased hip circumference (108.50(2.65 vs95.50(4.95, P=0.011) in male obese subjects. The study suggest that: There are diversity of variants in LepR gene among different race; and Lys109Arg, Gln223Arg, Lys656Asn variants in LepR gene were associated with some phenotypes in Chinese obese population, conferring minor effect for obesity.1) The genotypes of polymorphism in ob gene 3' flanking region were determined by PCR assay in 232 unrelated subjects of Chinese population ( including 130 simple obese people and 102 non-obese people). The clinical data were also analyzed. Results: No significant difference of genotype frequency of polymorphism in ob gene 3' flanking region was observed between obese and non-obese group. In obese group, "II" Allele was associated with increased waist/hip ratio (0.91(0.05 vs 0.86(0.03, P=0.047). This study suggested that: Polymorphism in ob gene 3' flanking region is associated with central obesity in Chinese obese population. 2) Individuals bearing all three polymorphisms ("II" allele in ob gene, "G" allele of Lys109Arg variant and "C" allele of Lys656Asn variant in LepR gene) were grouped as "A", this group was then compared to the remainder of the subjects (grouped as "B"). Result: "A" group had significantly higher BMI(31.42(0.85 vs 29.91(1.19, P=0.037) compared to group "B". This study suggested that:Minor effects may combine to associate with obesity.The genotypes of Pro12Ala variants in PPAR(-2 gene were determined by PCR-RFLP assay in 232 unrelated subj...
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