Based on the theory of constitution of Traditional Chinese Medicine （TCM）, the human population is divided into nine constitutions including one balanced constitution （Normality） and eight unbalanced constitutions...Based on the theory of constitution of Traditional Chinese Medicine （TCM）, the human population is divided into nine constitutions including one balanced constitution （Normality） and eight unbalanced constitutions （Yang-deficiency, Yin-deficiency, Phlegm-wetness, Qi-deficiency, Wetness-heat, Blood stasis, Depressed constitution, and Inherited special constitution）. Different constitutions have specific metabolic features and different susceptibility to certain diseases. However, whether a genetic basis accounts for such constitution classification is yet to be determined. Here we performed a genetic study to assess the association between genetic variations of metabolic genes including PPARD, PPARG and APM1 and the constitutions. A total of 233 individuals of the Han population in China were classified into four groups, Normality, Yang-deficiency, Yin-deficiency and Phlegm-wetness with whom 23 single nucleotide polymorphisms （SNPs） in the three genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method. Biased distribution of PPARD rs2267669 and rs2076167, APM1 rs7627128 and rs1063539 in Yang-deficiency, PPARG Prol2Ala in Yin-deficiency and PPARD rs2076167, APMI rs266729 and rs7627128 in Phlegm-wetness were observed. The frequencies of Haplotypel3 （Hapl3） of PPARG in Yin-deficiency, Hap25 of APM1 in Yang-deficiency and Hap2 of PPARD and Hapl4 of PPARG in Phlegm-wetness, were significantly different from those in Normality, suggesting those might be group-associated haplotypes. These results suggested that single SNP and haplotypes ofPPARD, PPARG and APM1 may underlie the genetic basis of the constitutions classified in TCM.展开更多
Background KCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds. The aim of this study was to test, in a Chinese Han population from B...Background KCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds. The aim of this study was to test, in a Chinese Han population from Beijing, whether the genetic variants in these four genes were associated with genetic predisposition to type 2 diabetes. Methods We studied the association of four representative SNPs in KCNJ11, ABCC8, PPARG, and HNF4A by genotyping them using ABI SNaPshot Multiplex System in 400 unrelated type 2 diabetic patients and 400 unrelated normoglycaemic subjects. Results rs5219（E23K） in KCNJ11 was associated with genetic susceptibility to type 2 diabetes （OR=1.400 with 95% CI 1.117 1.755, P=0.004 under an additive model, 0R=1.652 with 95% CI 1.086 2.513, P=0.019 under a recessive model, and OR=1.521 with 95% Cl 1.089 2.123, P=0.014 under a dominant model） after adjusting for sex and body mass index （BMI）. We did not find evidence of association for ABCC8 rs1799854, PPARG rs1801282 （Pro12Ala） and HNF4A rs2144908. Genotype-phenotype correlation analysis revealed that rs1799854 in ABCC8 was associated with 2-hour postprandial insulin secretion （P=0.005） after adjusting for sex, age and BMI. Although no interactions between the four variants on the risk of type 2 diabetes were detected, the multiplicative interaction between PPARG Pro12Ala and HNF4A rs2144908 was found to be associated with 2-hour postprandial insulin （P=-0.004 under an additive model for rs2144908; and P=0.001 under a dominant model for rs2144908） after adjusting for age, sex and BMI, assuming a dominant model for PPARG Pro12Ala. Conclusions Our study replicated the association of rs5219 in KCNJ11 with type 2 diabetes in Chinese Han population in Beijing. And we also observed that ABCC8 as well as the interaction between PPARG and HNF4A may contribute to post-challenge insulin secretion.展开更多
基金supported by the National Basic Research Program of China (973 Program) (No. 2005CB523501)
文摘Based on the theory of constitution of Traditional Chinese Medicine （TCM）, the human population is divided into nine constitutions including one balanced constitution （Normality） and eight unbalanced constitutions （Yang-deficiency, Yin-deficiency, Phlegm-wetness, Qi-deficiency, Wetness-heat, Blood stasis, Depressed constitution, and Inherited special constitution）. Different constitutions have specific metabolic features and different susceptibility to certain diseases. However, whether a genetic basis accounts for such constitution classification is yet to be determined. Here we performed a genetic study to assess the association between genetic variations of metabolic genes including PPARD, PPARG and APM1 and the constitutions. A total of 233 individuals of the Han population in China were classified into four groups, Normality, Yang-deficiency, Yin-deficiency and Phlegm-wetness with whom 23 single nucleotide polymorphisms （SNPs） in the three genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method. Biased distribution of PPARD rs2267669 and rs2076167, APM1 rs7627128 and rs1063539 in Yang-deficiency, PPARG Prol2Ala in Yin-deficiency and PPARD rs2076167, APMI rs266729 and rs7627128 in Phlegm-wetness were observed. The frequencies of Haplotypel3 （Hapl3） of PPARG in Yin-deficiency, Hap25 of APM1 in Yang-deficiency and Hap2 of PPARD and Hapl4 of PPARG in Phlegm-wetness, were significantly different from those in Normality, suggesting those might be group-associated haplotypes. These results suggested that single SNP and haplotypes ofPPARD, PPARG and APM1 may underlie the genetic basis of the constitutions classified in TCM.
文摘Background KCNJ11, ABCC8, PPARG, and HNF4A have been found to be associated with type 2 diabetes in populations with different genetic backgrounds. The aim of this study was to test, in a Chinese Han population from Beijing, whether the genetic variants in these four genes were associated with genetic predisposition to type 2 diabetes. Methods We studied the association of four representative SNPs in KCNJ11, ABCC8, PPARG, and HNF4A by genotyping them using ABI SNaPshot Multiplex System in 400 unrelated type 2 diabetic patients and 400 unrelated normoglycaemic subjects. Results rs5219（E23K） in KCNJ11 was associated with genetic susceptibility to type 2 diabetes （OR=1.400 with 95% CI 1.117 1.755, P=0.004 under an additive model, 0R=1.652 with 95% CI 1.086 2.513, P=0.019 under a recessive model, and OR=1.521 with 95% Cl 1.089 2.123, P=0.014 under a dominant model） after adjusting for sex and body mass index （BMI）. We did not find evidence of association for ABCC8 rs1799854, PPARG rs1801282 （Pro12Ala） and HNF4A rs2144908. Genotype-phenotype correlation analysis revealed that rs1799854 in ABCC8 was associated with 2-hour postprandial insulin secretion （P=0.005） after adjusting for sex, age and BMI. Although no interactions between the four variants on the risk of type 2 diabetes were detected, the multiplicative interaction between PPARG Pro12Ala and HNF4A rs2144908 was found to be associated with 2-hour postprandial insulin （P=-0.004 under an additive model for rs2144908; and P=0.001 under a dominant model for rs2144908） after adjusting for age, sex and BMI, assuming a dominant model for PPARG Pro12Ala. Conclusions Our study replicated the association of rs5219 in KCNJ11 with type 2 diabetes in Chinese Han population in Beijing. And we also observed that ABCC8 as well as the interaction between PPARG and HNF4A may contribute to post-challenge insulin secretion.
