***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: AIMS The beta-cell ATP-sensitive potassium channel consists of two subunits , SUR1 and Kir6.2 . Population association studies have shown that three variants in SUR1 and one in Kir6.2 are associated with Type 2 diabetes . These polymorphisms do not result in a functional change or affect splicing , suggesting that they could be in linkage disequilibrium with a pathogenic mutation . The present study aim ed firstly to screen the promoter regions of SUR1 and Kir6.2 to determine whether mutations in linkage disequilibrium with the silent variants lie in regulatory regions , which might lead to changes in gene expression . Secondly , novel and previously described variants associated with Type 2 diabetes ( SUR1 exon 16 - 3 t , exon 18 T , and Kir6.2 E23 K ) were investigated in the UKPDS cohort . METHODS The promoter sequences of both genes were screened by single-str and ed conformational polymorphism analysis for variants associated with Type 2 diabetes . The previously reported variants were evaluated in 364 Type 2 diabetic and 328 normoglycaemic control subjects . RESULTS Two variants were detected in the SUR1 promoter , a three base insertion ( caa ) at -522 bp and a single base substitution at - 679 bp ( c-->g ) . Neither of the variants were associated with diabetes , nor were they in a sequence consensus region for transcription factors . No association with diabetes was observed for either SUR1 variant . However , in contrast , analysis of the Kir6.2 E23 K variant showed that the KK homozygosity was more frequent in Type 2 diabetic than control subjects . Variants were not associated with clinical characteristics nor did they affect response to sulphonylurea therapy CONCLUSION There is no support at present for mutations in either Kir6.2 or SUR1 promoter sequences contributing to Type 2 diabetes . However , the minimal promoter region of SUR1 has yet to be investigated . The E23 K variant of Kir6.2 is associated with Type 2 diabetes mellitus in the UKPDS cohort Common genetic variants have been recently associated with fasting glucose and insulin levels in white population s. Whether these associations replicate in pre-diabetes is not known . We extended these findings to the Diabetes Prevention Program , a clinical trial in which participants at high risk for diabetes were r and omized to placebo , lifestyle modification or metformin for diabetes prevention . We genotyped previously reported polymorphisms ( or their proxies ) in/near G6PC2 , MTNR1B , GCK , DGKB , GCKR , ADCY5 , MADD , CRY2 , ADRA2A , FADS1 , PROX1 , SLC2A2 , GLIS3 , C2CD4B , IGF1 , and IRS1 in 3,548 Diabetes Prevention Program participants . We analyzed variants for association with baseline glycemic traits , incident diabetes and their interaction with response to metformin or lifestyle intervention . We replicated associations with fasting glucose at MTNR1B ( P<0.001 ) , G6PC2 ( P = 0.002 ) and GCKR ( P = 0.001 ) . We noted impaired β-cell function in carriers of glucose-raising alleles at MTNR1B ( P<0.001 ) , and an increase in the insulinogenic index for the glucose-raising allele at G6PC2 ( P<0.001 ) . The association of MTNR1B with fasting glucose and impaired β-cell function persisted at 1 year despite adjustment for the baseline trait , indicating a sustained deleterious effect at this locus . We also replicated the association of MADD with fasting proinsulin levels ( P<0.001 ) . We detected no significant impact of these variants on diabetes incidence or interaction with preventive interventions . The association of several polymorphisms with quantitative glycemic traits is replicated in a cohort of high-risk persons . These variants do not have a detectable impact on diabetes incidence or response to metformin or lifestyle modification in the Diabetes Prevention Program AIMS We aim ed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus ( T2DM ) patients . METHODS Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism . Forty-three patients with various genotypes were r and omly selected to undergo 8 weeks of repaglinide treatment ( 3 mg day(-1 ) ) . Fasting plasma glucose , postpr and ial plasma glucose , glycated haemoglobin , fasting and postpr and ial serum insulin ( FINS , PINS ) , homeostasis model assessment for insulin resistance , serum triglyceride , total cholesterol , low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment . RESULTS The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [ 13.45 vs. 6.82 % , P < 0.01 , odds ratios = 2.342 ( 1.365 , 4.019 ) , P= 0.002 ] . Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45 T polymorphism showed higher FINS ( 13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1 ) , P < 0.05 ) ( 11.67 , 14.83 vs. 8.38 , 11.37 ) and PINS ( 52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1 ) , P < 0.05 ) ( 44.89 , 58.35 vs. 55.35 , 88.87 ) than individuals with the T allele . The PAX4 R121W R allele carriers had higher PINS ( 52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1 ) , P < 0.05 ) ( 44.89 , 58.35 vs. 55.35 , 88.87 ) than subjects with the W allele . After repaglinide treatment , patients with the T allele of NeuroD1/BETA2 A45 T polymorphisms had attenuated efficacy on fasting plasma glucose ( -2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1 ) , P < 0.01 ) ( -3.53 , -1.84 vs.-1.99 , -0.13 ) and postpr and ial plasma glucose ( -6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1 ) , P < 0.01 ) ( -9.28 , -4.62 vs.-4.34 , -0.84 ) . Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postpr and ial plasma glucose than R/W genotypes ( -6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1 ) , P < 0.05 ) ( -8.20 , -4.89 vs.-3.92 , -1.20 ) . CONCLUSIONS The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy OBJECTIVE To investigate the influence of peroxisome proliferator-activated receptor-gamma ( PPAR-gamma ) gene variants on the response rate to therapy with the thiazolidinedione ( TZD ) pioglitazone , because in vitro studies have suggested that genetic variants of the PPAR-gamma gene may influence the drug efficacy of TZD . RESEARCH DESIGN AND METHODS A total of 131 patients were treated in an open-label , r and omized , multicenter study with pioglitazone ( 45 mg o.d . ) during a course of > or=26 weeks . Response to the pioglitazone therapy was defined by either a > 20 % decrease in fasting plasma glucose or a > 15 % decrease in HbA(1c ) values after 26 weeks of pioglitazone treatment . We evaluated the association between the PPAR-gamma genotype and the response rate to pioglitazone treatment . RESULTS The Pro12Ala and the Pro12Pro variants in the PPAR-gamma gene are not associated with the response rate to pioglitazone treatment in patients with type 2 diabetes . However , we identified initial fasting plasma glucose level > 11.0 mmol/l , HbA(1c ) value > 9.0 % , BMI > 32 kg/m(2 ) , and fasting C-peptide concentrations at baseline > 2.5 pmol/l as predominant confounding factors for the responder frequency to pioglitazone treatment . CONCLUSIONS The Pro12Ala variant in the PPAR-gamma gene does not affect the therapy efficacy of pioglitazone , suggesting that the drug-treatment response is independent from pharmacogenetic effects between PPAR-gamma and its lig and pioglitazone . Whether the Ala12Ala genotype plays a role in the response rate to TZD therapy remains to be determined Metformin is the most commonly used pharmacological therapy for type 2 diabetes . We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospect i ve Diabetes Study . In a combined meta- analysis , we identified a SNP , rs11212617 , associated with treatment success ( n = 3,920 , P = 2.9 × 10−9 , odds ratio = 1.35 , 95 % CI 1.22–1.49 ) at a locus containing ATM , the ataxia telangiectasia mutated gene . In a rat hepatoma cell line , inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in  response to metformin . We conclude that ATM , a gene known to be involved in DNA repair and cell cycle control , plays a role in the effect of metformin upstream of AMP-activated protein kinase , and variation in this gene alters glycemic response to metformin Aim : To investigate the influence of peroxisome proliferator-activated receptor γ2 ( PPAR-γ2 ) gene polymorphism rs1801282 and protein tyrosine phosphatase receptor type D ( PTPRD ) gene polymorphism rs17584499 on the occurrence of type 2 diabetes and pioglitazone efficacy in a Chinese Han population . Methods : One hundred ninety seven type 2 diabetes patients and 212 healthy controls were enrolled . Among them , 67 type 2 diabetes patients were administered pioglitazone ( 30 mg/d , po ) for 3 months . All the subjects were genotyped for genetic variants in PPAR-γ2 and PTPRD using MALDI-TOF mass spectrometry  . Fasting plasma glucose , postpr and ial plasma glucose , glycated hemoglobin , serum triglyceride , total cholesterol , low-density and high-density lipoprotein-cholesterol were determined . Results : The PPAR-γ2 gene rs1801282 polymorphism was significantly associated with type 2 diabetes susceptibility ( OR=0.515 , 95 % CI 0.268–0.990 ) and the PTPRD gene rs17584499 polymorphism was also significantly associated with type 2 diabetes ( OR=1.984 , 95 % CI 1.135–3.469 ) in a dominant model adjusted for age , gender and BMI . After pioglitazone treatment for 3 months , the type 2 diabetes patients with PPAR-γ2 rs1801282 CG genotypes significantly showed higher differential values of postpr and ial plasma glucose and serum triglyceride compared with those with rs1801282 CC genotype . The patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower differential value of postpr and ial plasma glucose compared to those with rs17584499 CC genotype . Conclusion : Diabetes risk alleles in PPAR-γ2 ( rs1801282 ) and PTPRD ( rs17584499 ) are associated with pioglitazone therapeutic efficacy The aim of this study was to examine the effects of the Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor ( PPAR ) γ2 gene on the response to rosiglitazone in patients with type 2 diabetes mellitus Objective Genome-wide association studies ( GWASs ) identified that SLC30A8 genetic polymorphism was a risk of type 2 diabetes mellitus ( T2DM ) in several 
    Output:
    
We found evidence of pharmacogenetic interactions for metformin , sulfonylureas , repaglinide , thiazolidinediones , and acarbose consistent with their pharmacokinetics and pharmacodynamics .