RESUMEN
OBJECTIVE: Zinc-α2-glycoprotein (ZAG) has been identified recently as a novel adipokine due to its close link with lipid and glucose metabolism, as well as regulation of body weight. The aim of our present study is to investigate the ZAG genetic polymorphism association with obesity in Chinese north Han population. DESIGN AND METHODS: Five SNPs of ZAG gene including rs2247607 (A>T), rs4727442 (G>T), rs4215 (A>G), rs2527923 (C>T) and rs2527882 (C>T) were genotyped in 648 overweight/obese patients and 313 healthy controls by TaqMan-PCR methods. Crosstabs statistical analysis method with subjects stratifying by age (⦠30 y, 31-45 y, ⧠46 y) and gender was used. RESULTS: The results showed the constitution of three genotype frequencies in rs4215 (A>G) site significantly differs in male subgroup (aged 31-45 y) between overweight/obese and healthy control group (χ(2)=6.401, P=0.041). GG genotype frequency in overweight/obese group is 19.3% which is much higher than 6.1% in healthy control group. Further statistical analysis under a recessive inheritance model demonstrated odd ratio (OR) for GG vs. AA+AG in overweight/obese group was 3.674 (95% CI 1.049-12.866; P=0.035). Among three genotypes of rs4215, the subjects with GG genotype have much more higher body weight, BMI, waist circumference and SBP. CONCLUSION: Our data, for the first time, suggest the genotypes of rs4215 in ZAG gene are significantly associated with obesity in Chinese north Han population. GG genotype subjects in rs4215 site have an increased susceptibility to obesity when compared with the AA+AG genotype subjects.
Asunto(s)
Adipoquinas/genética , Pueblo Asiatico/genética , Peso Corporal/genética , Obesidad/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas de Plasma Seminal/genética , Adulto , Secuencia de Bases , Pesos y Medidas Corporales , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADN , Zn-alfa-2-GlicoproteínaRESUMEN
CONTEXT: Myostatin (MSTN) is a member of the TGF-ß superfamily of signal transduction proteins, which plays an important role in muscular growth and lipid metabolism. OBJECTIVE: To study the association of myostatin gene polymorphisms with obesity in Chinese north Han human subjects. DESIGN: 297 healthy and 606 over-weight/obesity Chinese north Han subjects were selected as healthy control group and overweight/obesity group, respectively. The methods of DNA Sequencing, Restriction Fragment Length Polymorphism (RFLP) and TaqMan® probe were used to screen myostatin gene SNPs and clarify genotype in every individual. RESULTS: Total 11 SNPs in MSTN gene were identified by DNA sequencing and three SNPs including rs35781413 (G/A), rs3791783 (A/G) and rs3791782 (A/G) were selected for further study in total 903 samples. The results showed that the frequency of AA genotype of rs3791783 A/G SNP was significantly higher (56.4% vs. 50.8%) and the frequency GG genotype was significantly lower (3.2% vs. 6.7%) in overweight/obese patients than in normal weight subjects. A logistic regression analysis under a recessive inheritance model (AA+AG vs.GG) demonstrated that the Odd ratio for AA+AG vs.GG were 1.985 (95% CI 1.078-3.643; P=0.029). Among three genotypes of rs3791783, the subjects with AA genotype have much more higher body weight, BMI, waist circumference, TC, TG and LDL-C than those with GG genotype. CONCLUSIONS: Our data firstly suggest that genetic variant rs3791783 A/G in myostatin gene are associated with obesity. The A allele carriers in rs3791783 SNP have an increased susceptibility to obesity compared with the G allele carriers. Participants with AA genotype in rs3791783 SNP site will have higher risk suffered from overweight or obesity than those with GG genotype.