***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: Heading Abstract Objective . UDP-glucuronosyltransferase ( UGT ) 2B7 is the major UGT isoform responsible for the 3- and 6-glucuronidation of morphine in humans . Studies in rats have indicated that UGT1A1 may also contribute to the formation of morphine 3-glucuronide ( M3 G ) . Our objective was to investigate whether the UGT2B7 H268Y and UGT1A1 * 28 polymorphisms contribute to the variability in morphine glucuronide-to-morphine plasma ratios among cancer patients undergoing analgesic therapy with morphine . Methods . Seventy patients with normal hepatic and renal function using slow-release morphine to relieve cancer pain were included .  UGT2B7 genotyping was performed using restriction enzyme analysis of polymerase chain reaction (PCR)-amplified DNA fragments . Wild-type and variant alleles of the UGT1A1 gene were identified using sizing of PCR-amplified fragments . Morphine 6-glucuronide (M6G)/morphine , M3G/morphine , and M3G/M6 G plasma ratios were compared between genotypes . Results . The M3G/morphine , M6G/morphine , and M3G/M6 G plasma ratios varied 16- , 42- , and sevenfold , respectively , among individuals . No statistically significant differences in plasma ratios were found between individuals possessing UGT2B7 H/H ( n=20 ) , H/Y ( n=30 ) , or Y/Y ( n=20 ) genotypes . Five patients were homozygous for the UGT1A1 TA7 allele , which is associated with reduced UGT1A1 gene expression . However , the mean M3G/M6 G and M3G/morphine plasma ratios in TA7 homozygous subjects did not differ significantly from those of heterozygous or homozygous wild-type ( TA6 ) individuals . Conclusion . The UGT2B7 H268Y polymorphism can not account for the considerable variation in glucuronide-to-morphine ratios in cancer patients . Moreover , the contribution of UGT1A1 to the formation of M3 G appears to be of minor biological significance , at least in a UGT2B7 background Objective The CYP2D6 * 10 allele is the most common allele with a frequency ranging from 51.3 to 70 % and correlated with a significantly reduced metabolic activity in a Chinese population . The aim of the present study was to investigate whether the CYP2D6 * 10 allele has an impact on the postoperative analgesia effect of tramadol in Chinese patients recovering from major abdominal surgery . Methods A prospect i ve study design was used and 70 gastric cancer patients recovering from gastrectomy were enrolled . After receiving a loading dose i.v . , patients could self-administer doses of the drug combination ( 10 mg/ml tramadol plus 0.3 mg/ml metoclopramide ) via patient-controlled analgesia ( PCA ) . Blood sample s were collected after induction of anesthesia . The CYP2D6 * 10 C188 T polymorphism was analyzed by means of polymerase chain reaction-based restriction fragment length polymorphism ( PCR-RFLP ) . Demographic data among groups with different genotypes were analyzed using analysis of variance . The total consumption of tramadol  between the three genotype groups for 48 h was compared . Results The allele frequency of CYP2D6 * 10 is 52.4 % ; patients were categorized into three groups according to the CYP2D6 genotype : patients without CYP2D6 * 10 ( group I , n=17 ) , patients heterozygous for CYP2D6 * 10 ( group II , n=26 ) , and patients homozygous for CYP2D6 * 10 ( group III , n=20 ) . The demographic data among the three groups were comparable . The total consumption of tramadol for 48 h in group III was significantly higher than that in groups I and II , while it did not differ between groups I and II . Conclusions This study indicates that the CYP2D6 * 10 allele has significant impact on analgesia with tramadol in a Chinese population . Pharmacogenetics may explain some of the varying responses to pain medication in postoperative patients Purpose To investigate interindividual variability in response to pain treatment , we characterized postoperative patients for morphine metabolism and for COMT , OPRM1 and UGT2B7 polymorphisms . Methods A total of 109 patients treated with morphine  were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT , OPRM1 and UGT2B7 genes . The plasma concentration of morphine and of M3G/M6 G metabolites were evaluated by means of reversed phase high-performance liquid chromatography coupled with mass spectrometry . Results An association between average morphine consumption during the first 24 postoperative hours by patient-controlled analgesia ( PCA ) and COMT haplotypes was found . Specifically , patients with the diplotype for average pain intensity ( APS/APS ) required the lowest  morphine doses compared to the other subjects ( p = 0.011 ) . The APS haplotype contains an adenine corresponding to methionine , instead of valine , at position 158 of the COMT protein . Met/Met homozygous patients consumed significantly lower morphine doses than other subjects ( p = 0.014 ) ; accordingly , Val158Met genotyping alone might be used in the clinical setting to predict PCA morphine need . Considering both COMT Val158Met and OPRM1 A118 G polymorphisms , carriers of both the Met/Met and AA genotypes required less morphine than other subjects , although the difference was not significant . The analysis of UGT2B7 revealed the occurrence of two common haplotypes ( G_C_C_A_C and A_T_T_G_T ) that did not prove to be related with plasma morphine and M3G/M6 G concentration . Conclusions By considering COMT , OPRM1 , and UGT2B7 genotypes , as well as pharmacokinetic results , only COMT polymorphisms appear to be predictive of morphine need in postoperative pain therapy Background : Animal and human studies indicate that genetics may contribute to the variability of morphine efficacy . A recent report suggested that cancer patients homozygous for the 118 G allele caused by the single nucleotide polymorphism at nucleotide position 118 in the & mgr;-opioid receptor gene require higher doses of morphine to relieve pain . The purpose of the current study was to investigate whether this polymorphism contributes to the variability of morphine efficacy in women who undergo abdominal total hysterectomy . Methods : After informed consent was obtained , 80 female patients ( American Society of Anesthesiologist physical status I or II ) scheduled to undergo elective total hysterectomy surgery were enrolled in this study . All patients received general anesthesia  and were screened for A118 G polymorphism by blood sample . Intravenous morphine patient-controlled analgesia was provided postoperatively for satisfactory analgesia . The authors recorded the  morphine consumption doses and dem and times . Pain at rest and side effects were measured with rating scales . Results : Forty-three women were A118 homozygous , 19 were heterozygous , and 18 were G118 homozygous . Patients homozygous for G118 required more morphine doses ( 33 ± 10 mg ) to achieve adequate pain relief compared with patients homozygous for A118 ( 27 ± 10 mg ) in the first 24 h ( P = 0.02 ) . However , there was no statistically significant difference for morphine consumption at 48 h. Conclusion : Genetic variation of the & mgr;-opioid receptor may contribute to interindividual differences in postoperative morphine consumption . In the future , identifying single nucleotide polymorphisms of patients may provide information to modulate the analgesic dosage of opioid for better pain control Morphine is the analgesic of choice for moderate to severe cancer pain ; however , 10–30 % of patients do not tolerate morphine . This study evaluated genetic variation in the μ-opioid receptor , βarrestin2 , stat6 and uridine diphosphate-glucuronysltransferase 2B7 ( UGT2B7 ) genes , in patients who responded to morphine vs those who were switched to alternative opioids .  We prospect ively recruited and genotyped 162 Caucasian patients ( 117 controls , 39 switchers ) . Switchers , were more likely to carry the common allele at 1182 G/A , 5864 G/A , 8622T/C and 11143 G/A in the βarrestin2 gene ( P=0.021 , 0.043 , 0.013 , 0.043 , respectively ) . Switchers had increased carriage of the T allele ( −1714 C/T ) and a significant difference in the allelic frequency at 9065 C/T ( χ2=3.86 , P=0.049 ) in the stat6 gene . No differences were seen in genotype or allele frequencies of SNPs in the μ-opioid receptor gene or UGT2B7 gene . This study presents novel data suggesting that variation in genes involved in μ-opioid receptor signalling influence clinical response to morphine Objective This study examined whether the choice of pain-related outcome to represent opioid efficacy influenced findings in a genetic association study . Data from the European Pharmacogenetic Opioid Study , which used opioid dose as the outcome , were analysed in respect of six alternative outcomes : average pain intensity , pain right now , worst pain intensity , pain at its least , pain relief and pain interference . Design Cancer pain patients using an opioid for moderate or severe pain were included . The pain outcomes were obtained using the  Brief Pain Inventory . Genetic variation was analysed for 112 single nucleotide polymorphisms ( SNPs ) in 25 c and i date genes relevant for opioid efficacy . The patients were r and omly divided into a development and a validation sample and linear regression was used to compare the e quality of means in the six outcomes . The influence of non-genetic factors was controlled for , the regression analyses were stratified by country , and the results were corrected for multiple testing . Results 2201 cancer pain patients were included . Their mean age was 62.4 years and mean average pain was 3.5 . None of the examined SNPs exceeded p values corrected for multiple testing for any of the outcomes . Conclusions None of the outcomes were associated with variation in the selected SNPs , as previously shown for opioid dose . Thus , we observed that findings related to associations between genetic variability and opioid efficacy were consistent for several alternative outcomes 
    Output:
    
The results indicated that genetic variation of µ‑opioid receptor 1 ( OPRM1 ) may contribute to inter‑individual differences in morphine consumption with recommendation grade A for OPRM A118 G single nucleotide polymorphism ( rs1799971 ) .
Polymorphisms associated with the metabolization process of morphine and other opioid drugs are very relevant in opioid titration and ethnic subgroup differences which have to be taken into account ( particularly , for the recommendation grade A for the CYP2D6 polymorphism ) .
In human studies , the catechol‑O‑methyl transferase ( COMT ) genotype affects the efficacy of opioids in acute and chronic pain under different setting s , with recommendation grade B to the COMT single nucleotide polymorphism rs4680 ( Val/Met ) .