UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood / 中国中药杂志

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Anemoside B4 regulates fatty acid metabolism reprogramming in mice with colitis-associated cancer / 中国中药杂志

The study aimed to investigate the effect of anemoside B4(B4) on fatty acid metabolism in mice with colitis-associated cancer(CAC). The CAC model was established by azoxymethane(AOM)/dextran sodium sulfate(DSS) in mice. Mice were randomly divided into a normal group, a model group, and low-, medium-, and high-dose anemoside B4 groups. After the experiment, the length of the mouse colon and the size of the tumor were measured, and the pathological alterations in the mouse colon were observed using hematoxylin-eosin(HE) staining. The slices of the colon tumor were obtained for spatial metabolome analysis to analyze the distribution of fatty acid metabolism-related substances in the tumor. The mRNA levels of SREBP-1, FAS, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 were determined by real-time quantitative PCR(RT-qPCR). The results revealed that the model group showed decreased body weight(P<0.05) and colon length(P<0.001), increased number of tumors, and increased pathological score(P<0.01). Spatial metabolome analysis revealed that the content of fatty acids and their derivatives, carnitine, and phospholipid in the colon tumor was increased. RT-qPCR results indicated that fatty acid de novo synthesis and β-oxidation-related genes, such as SREBP-1, FASN, ACCα, SCD-1, ACOX, UCP-2, and CPT-1 mRNA expression levels increased considerably(P<0.05, P<0.001). After anemoside B4 administration, the colon length increased(P<0.01), and the number of tumors decreased in the high-dose anemoside B4 group(P<0.05). Additionally, spatial metabolome analysis showed that anemoside B4 could decrease the content of fatty acids and their derivatives, carnitine, and phospholipids in colon tumors. Meanwhile, anemoside B4 could also down-regulate the expression of FASN, ACCα, SCD-1, PPARα, ACOX, UCP-2, and CPT-1 in the colon(P<0.05, P<0.01, P<0.001). The findings of this study show that anemoside B4 may inhibit CAC via regulating fatty acid metabolism reprogramming.

Study on effect of anemoside B4 in improving COPD rats by regulating IL-12/STAT4 and IL-4/STAT6 signaling pathways / 中国中药杂志

To study the effect of anemoside B4 on rats with chronic obstructive pulmonary disease (COPD).Seventy-two SD male rats were randomly divided into blank group and model group.The method of exposure to cigarette smoke and combined with lipopolysaccharide (LPS) was used to replicate the rat model of COPD.After the model was maintained for 5 weeks,the rats were randomly divided into model group,dexamethasone group (0.81 mg·kg~(-1)) and anemoside B4 low,medium and high (2,4,8 mg·kg~(-1)) dose groups,a group of 12 animals were administered,and then the administration was started.The administration was maintained until the28th day,and the pulmonary function parameters of rats were measured by an animal pulmonary function instrument.After testing the rat lung function parameters,immediately draw rat alveolar lavage fluid (BALF),and use high-throughput protein chip technology to determined the expression levels of inflammatory cytokines in rat BALF.HE staining was used to observe the general pathological changes of rat lung and tracheal tissue.Masson staining was used to observe the collagen deposition in rat lung tissue.Real-time q PCR method was used to determine the mRNA expression level of related genes in rat lung tissue.Western blot method was used to determine the expression levels of related proteins in rat lung tissues.According to the findings,compared with the model group,the dexamethasone group and the anemoside B4 drug groups had different degrees of increase in the lung function parameters of rats (P<0.01,P<0.05),improved the expression level of inflammatory cytokines in the BALF of rats to varying degrees (P<0.01,P<0.05),and improved the pathological structure of rat lung tissue to varying degrees.Relative mRNA expressions of matrix metalloproteinase 2 (MMP-2),matrix metalloproteinase 12 (MMP-12),matrix metalloproteinase inhibitor 1 (TIMP-1),interleukin-6 (IL-6),and transforming growth factor-β1 (TGF-β1) were significantly reduced (P<0.01);whereas relative mRNA expressions of matrix metalloproteinase 9(MMP-9) and matrix metalloproteinase inhibitor 2 (TIMP-2) were increased significantly (P<0.01).The mRNA and protein expression levels of T-box transcription factor (T-bet),interleukin-12 (IL-12) and signal transducer and activator of transcription 4(STAT4) reduced to varying degrees (P<0.01,P<0.05).The mRNA of transcription factor GATA3 (binding protein-3),interleukin-4 (IL-4) and signal transducer and activator of transcription 6 (STAT6) in rat lung tissues and the protein expression levels of IL-4 and STAT6 were increased to varying degrees (P<0.01,P<0.05).In conclusion,anemoside B4 has a certain protective effect on COPD rats caused by cigarette smoke exposure and combined with LPS.The mechanism of action may be related to the regulation of IL-12/STAT4 and IL-4/STAT6 signaling pathways.

Therapeutic Effect of Anemoside B4 on Chronic Endometritis in Rats and Its Related Factors / 中国实验方剂学杂志

Objective:The effects of anemoside B4 on endometritis rats were studied through in vivo and in vitro experiments. Method:Animal experiments used 25% phenol glue to prepare endometritis models. 60 female SD rats were randomly divided into blank group， model group， Kushen gel group（0.005 g·kg-1），anemoside B4 gel low，medium and high dose groups（0.005，0.01，0.02 g·kg-1），10 rats in each group，except for the blank group，rats in each group were injected with 25% phenol glue into their vagina every 2 days，and the modeling continued for 30 days. Administration started on the day after modeling. Anemoside B4 gel low， medium and high dose groups were administered rectal daily，Kushen gel group was given daily vaginal administration. The blank group and model group were given the same amount of normal saline in the same way for 30 consecutive days. After the last administration，the uterus and its attachments of each group of rats were taken to analyze the uterine morphology and index. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of rat uterus. Real-time PCR was used to detect tumor necrosis factor-α （TNF-α），interleukin-1β （IL-1β），and interleukin-6 （IL-6），signal transduction protein 130 （gp130），signal transduction and transcription activator 3 （STAT3）mRNA expression. Detection of IL-6 and STAT3 protein expression in rat uterus by Western blot. In cell experiments，lipopolysaccharide （LPS）was used to induce rat endometrial epithelial cells to prepare an in vitro inflammation model， and Real-time PCR was used to detect the expression of IL-6，gp130 and STAT3 mRNA in each group of rat endometrial epithelial cells. Result:The results of animal experiments showed that compared with the blank group， the model group had inadequate uterine cavity adhesions， endometrial edema and hyperemia. Compared with model group， there was no adhesion in the uterine cavity of the rats in the high dose anemoside B4 gel group and the Kushen gel group. The uterine tissue was relatively complete， and the uterine pathological structure was significantly improved. Compared with the blank group， the uterine index of the model group was significantly increased（P<0.05）， the expression of IL-1β mRNA in the uterine tissue was significantly increased （P<0.05）， the expression of mRNA and protein of IL-6 and STAT3 in the uterine tissue significantly increased （P<0.05）. Compared with model group， the uterine index in anemoside B4 gel high dose group was significantly reduced （P<0.05）， and the mRNA and protein expression levels of IL-6 and STAT3 in the uterine tissue were significantly reduced （P<0.05）. There was no statistically significant difference between the TNF-α and IL-1β mRNA expression compared with the model group. Cell experiment results showed that compared with the blank group， the mRNA expression of IL-6 and gp130 in model group endometrial epithelial cells was significantly increased （P<0.01）， STAT3 mRNA expression was significantly increased （P<0.05）. Compared with model group， the mRNA expression levels of IL-6， gp130 and STAT3 in anemoside B4 high dose group decreased significantly （P<0.05）. Conclusion:Anemoside B4 can improve the inflammatory response of chronic endometritis in rats and reduce the release of inflammatory factor IL-6. The mechanism may be related to the down-regulation of IL-6/STAT3 pathway.

Effect of Saponins in Pulsatillae Radix on Proliferation and Apoptosis of NCI-H460 Lung Cancer Cells and Screening of Its Differentially Expressed Proteins / 中国实验方剂学杂志

Objective: To screen the differentially expressed proteins of saponins in Pulsatillae Radix inhibiting the proliferation and induce apoptosis on NCI-H460 tumor cells based on proteome technology using nano LC-LTQ-Orbitrap-MS/MS, and preliminarily speculate the potential mechanism. Method: NCI-H460, SK-OV-3 and SGC-7901 tumor cells were cultured in vitro. Methylthiazoletetrazolium (MTT) assay was used to detect the inhibitory rate of saponins in Pulsatillae Radix on three tumor cell lines. Effect of saponins in Pulsatillae Radix on apoptosis was analyzed by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining flow cytometry and 4',6-diamidino-2-phenylindole (DAPI) staining. Apoptosis was analyzed using flow cytometry and DAPI stain. Nano LC-LTQ-Orbitrap-MS/MS was used to investigate the changes in the protein profiles on NCI-H460 cells treated with saponins in Pulsatillae Radix. Proteins exhibiting differential expression were analyzed by DAVID Bioinformatics Resources 6.8 and Kyoto encyclopedia of genes and genomes (KEGG) database. The differentially expressed proteins were verified by Western blot. Result: Saponins in Pulsatillae Radix could inhibit the proliferation of NCI-H460, SK-OV-3 and SGC-7901 tumor cells and induce apoptosis of NCI-H460 tumor cells. Effect of Saponins in Pulsatillae Radix on the proliferation and apoptosis of NCI-H460 tumor cells was mainly related to the regulation of biological function of ribosome, glycolysis/gluconeogenesis and other biological processes. It was possible to induce apoptosis of NCI-H460 tumor cells by interfering mitogen-activated protein kinase (MAPK) signaling pathway and regulating the Caspase pathway. Conclusion: Saponins in Pulsatillae Radix can inhibit the proliferation and induce the apoptosis of NCI-H460 tumor cells, the mechanism may be related to the intervention of MAPK signaling pathway and the regulation of Caspase pathway. These findings are helpful to elucidate the molecular mechanism of the anti-tumor effect of saponins in Pulsatillae Radix.

Analysis of clinical features of 23 patients with POEMS syndrome / 北京大学学报(医学版)

Objective:To describe the endocrine abnormalities in patients with POEMS syndrome in order to identify more patients with POEMS syndrome among those who have endocrine dysfunctions.Methods:We searched the inpatient medical record system of Peking University People's Hospital with "POEMS syndrome".Finally the data from 23 patients were analyzed.Epidata 3.0 was used for data entering and SPSS 19.0 was used for statistical analysis.Results:The median age of all the 23 patients was 47 years.The ratio of male to female was 1.88 ∶ 1.Polyneuropathy was the most common initial symptom which accounted for 56.5 ％ in the 23 patients.The median duration from the initial symptoms to diagnosis as POEMS syndrome was 30 months.Among all the departments,the number of confirmed cases was highest in the department of neurology.The median duration from the onset of initial symptoms (6 months) to the diagnosis made in neurology department was also significantly shorter than in other departments.Among all the 23 patients,100.0％ of them had polyneuropathy,82.6％ had organomegaly,95.7％ had endocrinopathy,52.2％ were M protein positive,91.3％ had skin changes,45.5％ had papilledema,43.5％ had extravascular volume overload,43.5％ had platelet elevation and 17.4％ had Castleman disease.Among all the patients with endocrinopathy,the incidence of hyperprolactinemia was 60.0％ which was the highest one followed by thyroid dysfunction and adrenal dysfunction.Among the patients who had endocrine system dysfunctions,most of them had two target endocrine glands involved (36.5％).Conclusion:Endocrinopathy is an important component of POEMS syndrome and it is of great importance to pay more attention to POEMS syndrome in patients with thyroid dysfunction,adrenal dysfunction,gonadal dysfunction,parathyroid dysfunction,hyperprolactinemia and glucose intolerance,especially in patients with two or more target gland dysfunctions.Symptoms and signs of polyneuropathy should be assessed carefully to reduce misdiagnosis of POEMS syndrome.Evaluation of the endocrine system should also be done in patients diagnosed with POEMS syndrome in order to treat the patients properly.

Relationship Between Serum Zinc Level and Microvascular Complications in Patients with Type 2 Diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies suggested that zinc level was related to a certain diabetic microvascular complication. However, the relationship between zinc level and all the microvascular complications in type 2 diabetic patients remains unknown. The purpose of this study was to analyze the relationship between zinc level and each diabetic microvascular complication and identify the features related to low serum zinc level.</p><p><b>METHODS</b>We included the hospitalized patients with type 2 diabetes (T2D) at our department from May 30, 2013 to March 31, 2014. We initially compared the serum zinc levels between patients with specific microvascular complications and those without. We then analyzed the association between zinc level and each microvascular complication. Furthermore, we identified the unique features of patients with high and low serum zinc levels and analyzed the risk factors related to low zinc level.</p><p><b>RESULTS</b>The 412 patients included 271 with microvascular complications and 141 without any microvascular complications. Serum zinc level was significantly lower in patients with diabetic retinopathy (P < 0.001), diabetic nephropathy (DN, P < 0.001), or diabetic peripheral neuropathy (P = 0.002) compared with patients without that specific complication. Lower zinc level was an independent risk factor for DN (odds ratio = 0.869, 95% confidence interval = 0.765-0.987, P < 0.05). The subjects with lower serum zinc level had manifested a longer duration of diabetes, higher level of hemoglobin A1c, higher prevalence of hypertension and microvascular complications, and lower fasting and 2-h C-peptide levels.</p><p><b>CONCLUSIONS</b>Lower serum zinc level in T2D patients was related to higher prevalence of diabetic microvascular complications, and represented as an independent risk factor for DN. Patients with lower zinc level were more likely to have a longer duration of diabetes, poorer glucose control, and worse β-cell function.</p>

Regulation of saponins from Pulsatilla chinensis on energy metabolism of Bel-7402 xenograft in nude mice / 中草药

Objective: To investigate the antirumour activity of saponins from Pulsatilla chinensis against the Bel-7402 human hepatocellular carcinoma xenograft in nude mice, and to explore the mechanism of energy metabolism. Methods: The antitumor activity in vivo was estimated using a Bel-7402 xenograft model. The tumor volume was measured, the tumor inhibitory rate was calculated, the levels of lactic acid and ATP were assessed in Bel-7402 xenograft in nude mice, energy metabolic enzymes in Bel-7402 xenograft in nude mice were detected by ELISA assay, and hypoxia inducible factor-1 (HIF-1α) was detected by Western blotting assay. Results: The sapoinins from P. chinensis could inhibit the growth of Bel-7402 xenograft in a dose-depedent manner. The tumor inhibitory rates at the dose of 400, 200, and 100 mg/kg were 42.8%, 31.5%, and 14.9%. They had no side effects on white blood cell (WBC) in blood; The saponins from P. chinensis could decrease the contents of lactic acid and ATP. They also could decrease the levels of glycolytic enzymes phosphofructokinase (PFK), hexokinase-II (HK-II), and pyruvate kinase (PK), while increase the level of succinatedehydrogenase (SDH) that was the key enzyme during tricarboxylic acid cycle. Western blotting indicated that the expression of HIF-1α protein was significantly decreased in Bel-7402 xenograft in nude mice. Conclusion: The saponins from P. chinensis could inhibit the growth of Bel-7402 xenograft in nude mice in vivo, the mechanism is related with regulating energy metabolism through the HIF-1α pathway.

Efficacy and safety of insulin treatment in type 2 diabetes using a new index called glucose safety control index / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To recommend an index named glucose safety control index (GSCI) to evaluate the efficacy and safety for insulin regimens.</p><p><b>DATA SOURCES</b>We searched databases for primary studies published in English. The main search concepts were type 2 diabetes, insulin treatment, premixed insulin, premixed insulin analogs, basal inuslin, basal inuslin analogs, bolus insulin, bolus insulin analogs, safety and efficacy.</p><p><b>STUDY SELECTION</b>Studies were eligible for inclusion if they met all of the following criteria: (1) type 2 diabetic patients aged >18 years were included; (2) random control studies with at least 12 weeks of follow-up; (3) different insulin regimens were evaluated.</p><p><b>RESULTS</b>When long-acting basal insulin therapy compared with neutral protamine Hagedorn (NPH) insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 100%, the proportion of GSCIΔA1c ratio more than 1 was 94.44%. When premixed insulin therapy compared with oral hypoglycemic agents plus basal insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 45.5%, the proportion of GSCIΔA1c ratio more than 1 was 38.9%. When premixed insulin therapy compared with oral hypoglycemic agents, the proportion of GSCI%A1c ratio less than 1 was 100%, the proportion of GSCIΔA1c ratio more than 1 was 50%. When premixed insulin therapy compared with basal-bolus insulin therapy, the proportion of GSCI%A1c ratio more than 1 was 37.5%, the proportion of GSCIΔA1c ratio more than 1 was 50%.</p><p><b>CONCLUSION</b>According to the GSCI ratio, long-acting basal insulin therapy tended to be superior to NPH therapy, oral hypoglycemic agents plus basal insulin therapy tended to be superior to premixed insulin therapy, noninsulin antidiabetic agents and premixed insulin therapy was comparable, and basal-bolus insulin therapy tended to be superior to premixed insulin therapy in type 2 diabetes.</p>

Contribution of the Akt2 gene to type 2 diabetes in the Chinese Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process. Akt2 is suggested to play a role in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass. In order to determine whether the Akt2 gene plays a role in the pathogenesis of type 2 diabetes characterized by insulin resistance, and to further identify if variations in this gene have a relationship with type 2 diabetes, we sequenced the entire coding region and splice junctions of Akt2 and made a further case-control study to explore the association between single-nucleotide polymorphisms (SNPs) in this gene and type 2 diabetes in the Chinese Han population.</p><p><b>METHODS</b>We selected 23 probands with a type 2 diabetic pedigree whose family members' average onset age was within 25 to 45 years old. The body mass index of all the participants was lower than 28 kg/m(2) and all of them were insulin-resistant (the fasting insulin level > 100 pmol/L or 16 µIU/ml). The entire coding region and splice junctions of Akt2 were directly sequenced in these 23 probands. SNPs with a frequency of minor allele over 20 percent were selected to be further studied in a case-control study. We chose 743 non-diabetic subjects as the control group and 742 type 2 diabetic patients as the case group. All these subjects were genotyped. A Snapshot Technology Platform (Applied Biosystems) was used for genotyping.</p><p><b>RESULTS</b>The Akt2 genes from all 23 subjects were successfully sequenced. We did not identify any mutation in the type 2 diabetic pedigree. Two SNPs were identified, 13010323T > C and 13007939G > T. 13010323T > C was in intron 9, which was the location of rs2304188 reported in Genbank. Its minor allele frequency was 13.04%. 13007939G > T was in the 3'-untranslated region (UTR) of exon 14, which was the location of rs2304186 reported in Genbank. Its minor allele frequency was 34.78%. The allele frequency of rs2304188 and rs2304186 were consistent with the frequency reported in Genbank. In the case-control study with 742 patients and 743 controls, there was no significant difference between the two groups for the allele frequency of rs2304186 (odd ratio: 0.96, 95% confidence interval: 0.82 - 1.12, P = 0.597).</p><p><b>CONCLUSIONS</b>The Akt2 gene is not a major cause of diabetes in a non-obese Chinese Han population characterized by insulin resistance. There is no significant relationship between rs2304186 and type 2 diabetes in the Chinese Han population.</p>

HLA-DQ, DR allele polymorphism of type 1 diabetes in the Chinese population: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Type 1 diabetes (T1D) is a multifactorial disease. This article aims to evaluate the relationship between allele polymorphism of HLA-DQ, DR and T1D in the Chinese population.</p><p><b>METHODS</b>The odds ratios (ORs) of HLA-DQ, DR allele distributions in patients with T1D were analyzed against healthy controls. All the relevant studies in Pubmed and CNKI were identified, and poor qualified studies were excluded. The meta-analysis software REVMAN 4.2 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. The publication bias were also evaluated.</p><p><b>RESULTS</b>DQA1*0301, DQA1*0501, DQB1*0201, DQB1*0302 were the susceptible alleles (all P < 0.05) in the Chinese population, their merger ORs 2.40, 3.15, 3.66, and 2.67 respectively. DQA1*0103, DQA1*0201, DQA1*0401, DQB1*0301, DQB1*0402, DQB1*0501, DQB1*0503, DQB1*0601 and DQB1*0602 were the protective alleles (P < 0.05), their merger ORs were 0.11, 0.45, 0.30, 0.38, 0.23, 0.37, 0.25, 0.48, and 0.30 respectively. In serum level, DR3, DR4, DR9 alleles were the susceptible alleles (all P < 0.05) and their merger ORs were 5.58, 1.53, 1.66, 29.78, and 6.65 respectively. HLA-DR2, DR5, and DR7 alleles were the protective alleles (all P < 0.05) and their merger ORs were 0.39, 0.51, and 0.50. In genetic type level, DRB1*04, DRB1*0301, DRB1*0901 were the susceptible alleles (all P < 0.05) and their merger ORs were 2.19, 6.43, 1.31, 3.83, and 8.08. DRB1*07, DRB1*08, DRB1*12, DRB1*13, DRB1*14, DRB1*16, DRB1*0406 alleles were the protective alleles (all P < 0.05) and their merger ORs were 0.44, 0.27, 0.45, 0.13, 0.19, 0.40, and 0.27 respectively.</p><p><b>CONCLUSIONS</b>In the Chinese population, some HLA-DQ, DR alleles are relevant to T1D which are not totally the same as non-Chinese populations.</p>

Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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, OR = 1.652 with 95% CI 1.086 2.513, P = 0.019 under a recessive model, and OR = 1.521 with 95% CI 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.</p><p><b>CONCLUSIONS</b>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.</p>