To the editor： Systemic lupus erythematosus （SLE） is a prototypic autoimmune disease with complex genetic inheritance.l In recent years, genome-wide association studies （GWAS） had further provided novel insights ...To the editor： Systemic lupus erythematosus （SLE） is a prototypic autoimmune disease with complex genetic inheritance.l In recent years, genome-wide association studies （GWAS） had further provided novel insights into the genetics background of SLE by identifying multiple susceptibility genes in different ethnic populations.展开更多
Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha （ERα） gene （also named ESR1）, including the ...Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha （ERα） gene （also named ESR1）, including the XbaⅠ and PvuⅡ restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ER0t gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level. Methods Two hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51--70 years. ESR1 genotyping was performed using polymerase chain reaction （PCR） and PvulI and XbaI restriction fragment length polymorphism （PCR-RFLP） analysis. Results ESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuⅡ, but not XbaⅠ, allele frequency between the type 2 diabetes mellitus and control groups （P=0.001 and P=0.122）. When the group was separated into men and women, the difference was significant in women （P〈0.001） but not in men （P=0.854） with the PvulI genotype, and the effect of PvulI variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvulI genotype was associated with blood glucose [fasting blood glucose （FBG）, postprandial blood glucose （PBG）] and serum lipid [total cholesterol （TC） and low density lipoprotein （LDL）-c] concentration in healthy women. Conclusions PvuII polymorphism of ESRI increases susceptibifity to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.展开更多
Background Some single nucleotide polymorphisms （SNPs） in the peroxisome proliferator-activated receptor-y coactivator （PGC）-1α gene have been reported to be associated with type 2 diabetes in different populatio...Background Some single nucleotide polymorphisms （SNPs） in the peroxisome proliferator-activated receptor-y coactivator （PGC）-1α gene have been reported to be associated with type 2 diabetes in different populations, and studies on Chinese patients yielded controversial results. The objective of this case-control study was to explore the relationship between SNPs of PGC-1α and type 2 diabetes in the southern Chinese population and to determine whether the common variants： Gly482Ser and Thr394Thr, in the PGC-1α gene have any impacts on interaction with myocyte enhancer factor （MEF） 2C. Methods The SNPs in all exons of the PGC-1α gene was investigated in 50 type 2 diabetic patients using polymerase chain reaction-single strand conformational polymorphism （PCR-SSCP） and direct sequencing. Thereafter, 263 type 2 diabetic patients and 282 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. A bacterial two-hybrid system and site-directed mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in the PGC-1α gene alter the interaction with MEF2C. Results Three frequent SNPs （Thr394Thr, Gly482Ser and Thr528Thr） were found in exons of the PGC-1α gene. Only the Gly482Ser variant had a different distribution between diabetic patients and healthy subjects, with the 482Ser allele more frequent in patients than in controls （40.1% vs 29.3%, P〈0.01）. Even in controls, the 482Ser（A） carriers were more likely to have higher levels of total cholesterol and low-density lipoprotein cholesterol than the 482Gly（G） carriers. The 394A-482G-528A haplotype was associated with protection from diabetes, while the 394A-482A-528A was associated with the susceptibility to diabetes. The bacterial two-hybrid system and site-directed mutagenesis revealed that the 482Ser variant was less efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr （A） had a synergic effect on the interaction between 482Ser variant and MEF2C. Conclusions The results suggested that the 482Ser variant of PGC-1α conferred the susceptibility to type 2 diabetes in the southern Chinese population. The underlying mechanism may be attributable, at least in part, to the altered interaction between the different variants （Gly482Ser, Thr394Thr） in the PGC-1α gene and MEF2C.展开更多
文摘To the editor： Systemic lupus erythematosus （SLE） is a prototypic autoimmune disease with complex genetic inheritance.l In recent years, genome-wide association studies （GWAS） had further provided novel insights into the genetics background of SLE by identifying multiple susceptibility genes in different ethnic populations.
文摘Background Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha （ERα） gene （also named ESR1）, including the XbaⅠ and PvuⅡ restriction enzyme polymorphisms of ESR1, which may be involved in disease pathogenesis. The aim of this study was to determine whether ER0t gene polymorphisms are associated with type 2 diabetes mellitus and serum lipid level. Methods Two hundred and ninety-nine patients with type 2 diabetes mellitus were compared with three hundred and forty-one health controls of Guangzhou in China, both were male and postmenopausal female residents at 51--70 years. ESR1 genotyping was performed using polymerase chain reaction （PCR） and PvulI and XbaI restriction fragment length polymorphism （PCR-RFLP） analysis. Results ESR1 allelic frequencies of P, p and X, x alleles were 0.408, 0.592; 0.360, 0.640 in the type 2 diabetes mellitus group and 0.318, 0.682; 0.328, 0.672 in the control group, respectively. In case-control study, there was significant difference in PvuⅡ, but not XbaⅠ, allele frequency between the type 2 diabetes mellitus and control groups （P=0.001 and P=0.122）. When the group was separated into men and women, the difference was significant in women （P〈0.001） but not in men （P=0.854） with the PvulI genotype, and the effect of PvulI variant on the development of type 2 diabetes mellitus was improved with aging. In addition, PvulI genotype was associated with blood glucose [fasting blood glucose （FBG）, postprandial blood glucose （PBG）] and serum lipid [total cholesterol （TC） and low density lipoprotein （LDL）-c] concentration in healthy women. Conclusions PvuII polymorphism of ESRI increases susceptibifity to type 2 diabetes mellitus in Chinese Guangzhou women. ESR1 variants may also impact serum lipid metabolism, which might provide a mechanism connecting ESR1 to type 2 diabetes.
文摘Background Some single nucleotide polymorphisms （SNPs） in the peroxisome proliferator-activated receptor-y coactivator （PGC）-1α gene have been reported to be associated with type 2 diabetes in different populations, and studies on Chinese patients yielded controversial results. The objective of this case-control study was to explore the relationship between SNPs of PGC-1α and type 2 diabetes in the southern Chinese population and to determine whether the common variants： Gly482Ser and Thr394Thr, in the PGC-1α gene have any impacts on interaction with myocyte enhancer factor （MEF） 2C. Methods The SNPs in all exons of the PGC-1α gene was investigated in 50 type 2 diabetic patients using polymerase chain reaction-single strand conformational polymorphism （PCR-SSCP） and direct sequencing. Thereafter, 263 type 2 diabetic patients and 282 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. A bacterial two-hybrid system and site-directed mutagenesis were used to investigate whether Gly482Ser and Thr394Thr variants in the PGC-1α gene alter the interaction with MEF2C. Results Three frequent SNPs （Thr394Thr, Gly482Ser and Thr528Thr） were found in exons of the PGC-1α gene. Only the Gly482Ser variant had a different distribution between diabetic patients and healthy subjects, with the 482Ser allele more frequent in patients than in controls （40.1% vs 29.3%, P〈0.01）. Even in controls, the 482Ser（A） carriers were more likely to have higher levels of total cholesterol and low-density lipoprotein cholesterol than the 482Gly（G） carriers. The 394A-482G-528A haplotype was associated with protection from diabetes, while the 394A-482A-528A was associated with the susceptibility to diabetes. The bacterial two-hybrid system and site-directed mutagenesis revealed that the 482Ser variant was less efficient than the 482Gly variant to interact with MEF2C, whereas the 394Thr （A） had a synergic effect on the interaction between 482Ser variant and MEF2C. Conclusions The results suggested that the 482Ser variant of PGC-1α conferred the susceptibility to type 2 diabetes in the southern Chinese population. The underlying mechanism may be attributable, at least in part, to the altered interaction between the different variants （Gly482Ser, Thr394Thr） in the PGC-1α gene and MEF2C.
