Association of the OPRM1 variant rs1799971 (A118G) and clinical manifestations in tramadol poisoned patients: a cross-sectional study.

INTRODUCTION: The opioid receptor mu1 is a protein coding gene that can have different codes for a protein and may have variations (polymorphisms) affecting how opioids work. The aim of this study was to investigate the prevalence of the most common opioid receptor mu1 polymorphism (A118G) and any relationship between this polymorphism and features following tramadol overdose. MATERIALS AND METHODS: This was a cross-sectional study of patients admitted with tramadol poisoning to an Iranian hospital. These patients were not taking any other drugs or medications and had no history of seizures. RESULTS: The results showed that among the 83 patients included in the study, 57 (69 per cent) had the AA genotype, 25 (30 per cent) had the AG genotype, and one (1 per cent) had the GG genotype for the opioid receptor mu1 A118G polymorphism. Nausea and/or vomiting occurred in nine (11 per cent) patients and dizziness in 38 (46 per cent) patients. Serious adverse events included seizures in 51 (60 per cent) patients and respiratory failure requiring mechanical ventilation in 21 (25 per cent) patients. However, there was no significant association between the opioid receptor mu1 A118G polymorphism and these adverse events. DISCUSSION: In our study, the frequency of the A allele was greater than the G allele, and the AA genotype was more prevalent than AG. The GG genotype was the least common among the polymorphisms of opioid receptor mu1 rs1799971. There was no significant association between the opioid receptor mu1 A118G polymorphism and symptoms in tramadol-poisoned patients. Although these allele proportions are similar to the results reported in other Caucasian populations, they are dissimilar to the findings in Chinese and Singaporean populations. In these Asian studies, the predominant allele was the G allele. It has been suggested that a mutated G allele will decrease the production of opioid receptor mu1-related messenger ribonucleic acid and related proteins, leading to fewer mu-opioid receptors in the brain. CONCLUSIONS: This study found no significant association between the opioid receptor mu1 A118G polymorphism and adverse outcomes in tramadol-poisoned patients. However, more research is needed to draw more definitive conclusions due to the limited evidence and variability of opioid receptor mu1 polymorphisms in different populations.

A randomized trial evaluating the association between related gene polymorphism and nausea and vomiting induced by cisplatin multi-day chemotherapy.

PURPOSE: We aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen. METHODS: Before chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0-24 h), the delayed phase (25-120 h) and the overall phase (0-120 h). RESULTS: Univariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05). CONCLUSION: This study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.

[Aldehyde dehydrogenase 2 rs671 genetic polymorphisms are associated with chemotherapy-induced nausea and vomiting].

OBJECTIVE: To investigate the correlation between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and chemotherapy-induced nausea and vomiting (CINV). METHODS: A total of 90 Chinese patients with malignant tumors receiving chemotherapy for the first time were recruited in this study. The occurrence of CINV was observed within 120 h after treatment with docetaxel and cis-platinum chemotherapy (DP regimen). The data of the patients (including age, gender, tumor stage, habitual alcohol consumption, motion sickness, morning sickness, and average sleep time prior to chemotherapy) were collected through a questionnaire. ALDH2 rs671 polymorphisms of the patients were analyzed using a multiple single nucleotide polymorphism genotyping, and the Hardy-Weinberg equation was used for genetic linkage analysis. The correlations between the factors including ALDH2 rs671 polymorphisms and the occurrence of CINV were analyzed. RESULTS: The incidence of CINV was 48.9% among the patients receiving their first chemotherapy with DP regimen. Univariate analysis indicated that the genetic polymorphisms of ALDH2 rs671 were significantly correlated with the occurrence of CINV (P < 0.05). Multivariate logistic analysis indicated that ALDH2 rs671 mutation (OR: 3.019, 95% CI: 1.056-8.628, P < 0.05) and average sleep time prior to chemotherapy no longer than 6 h (OR: 2.807, 95% CI: 1.033-7.628, P < 0.05) were risk factors for CINV in patients with malignant tumors receiving the first chemotherapy with DP regimen. CONCLUSION: ALDH2 gene mutation at rs671 is a risk factor contributing to the occurrence of CINV, and understanding of the underlying mechanism may help to more effectively control the occurrence of CINV.

Evaluation of nausea and vomiting in the first trimester on the risk of adverse birth outcomes and the contribution of genetic polymorphisms: a pilot prospective study.

PURPOSE: To evaluate the impact of Nausea and Vomiting in Pregnancy (NVP) on the risk of Preterm Birth (PTB) and Low Birth Weight (LBW), and explore the effect of genetic polymorphisms on the severity of NVP. METHODS: A prospective study was conducted. Participants' experience of NVP prior to 12 gestational weeks were evaluated by a Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scale. 11 Single Nucleotide Polymorphisms (SNPs) loci located in growth differentiation factor 15 (GDF15) and leucine-rich repeat containing 25 (LRRC25) gene of chr19p13.11 and intergenic region of chr4q12 were genotyped, which were implicated as genetic risk factors for NVP. Logistic regression models were applied to determine the effect of NVP in the first trimester on the risk of PTB and LBW, and genetic polymorphisms on the risk of NVP. RESULTS: Among 413 pregnant women, the incidence of nausea and vomiting was 85.5% (n = 353) in the first trimester, including 38.7% (n = 160) mild vomiting, 42.6% (n = 176) moderate vomiting and 4.1% (n = 17) severe vomiting. 33 were PTB, 20 were LBW. Compared with pregnant women without NVP, women with mild, moderate or severe NVP in the first trimester were not associated with the risk of PTB and LBW. Besides, the polymorphisms of 11 SNPs loci were not associated with the risk of NVP. CONCLUSIONS: Our study indicated that symptoms of nausea and vomiting in the first trimester were not significantly associated with PTB and LBW, and there were also no associations between GDF15 and LRRC25 polymorphisms and NVP.

Aldehyde dehydrogenase 2 rs671 genetic polymorphisms are associated with chemotherapy-induced nausea and vomiting / 南方医科大学学报

OBJECTIVE@#To investigate the correlation between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and chemotherapy-induced nausea and vomiting (CINV).@*METHODS@#A total of 90 Chinese patients with malignant tumors receiving chemotherapy for the first time were recruited in this study. The occurrence of CINV was observed within 120 h after treatment with docetaxel and cis-platinum chemotherapy (DP regimen). The data of the patients (including age, gender, tumor stage, habitual alcohol consumption, motion sickness, morning sickness, and average sleep time prior to chemotherapy) were collected through a questionnaire. ALDH2 rs671 polymorphisms of the patients were analyzed using a multiple single nucleotide polymorphism genotyping, and the Hardy-Weinberg equation was used for genetic linkage analysis. The correlations between the factors including ALDH2 rs671 polymorphisms and the occurrence of CINV were analyzed.@*RESULTS@#The incidence of CINV was 48.9% among the patients receiving their first chemotherapy with DP regimen. Univariate analysis indicated that the genetic polymorphisms of ALDH2 rs671 were significantly correlated with the occurrence of CINV (P < 0.05). Multivariate logistic analysis indicated that ALDH2 rs671 mutation (OR: 3.019, 95% CI: 1.056-8.628, P < 0.05) and average sleep time prior to chemotherapy no longer than 6 h (OR: 2.807, 95% CI: 1.033-7.628, P < 0.05) were risk factors for CINV in patients with malignant tumors receiving the first chemotherapy with DP regimen.@*CONCLUSION@#ALDH2 gene mutation at rs671 is a risk factor contributing to the occurrence of CINV, and understanding of the underlying mechanism may help to more effectively control the occurrence of CINV.

[A Case of Congenital Tufting Enteropathy with EpCAM Gene Complex Heterozygous Mutation (c.491+1G>A; c.352_353ins CACC)].

The patient, a one-month-old male infant, was admitted for "recurrent diarrhea for 20 + days and vomiting for 4 days". On the 8th day after birth, the patient began to develop recurrent refractory diarrhea, accompanied by abdominal distension, vomiting, dehydration, acidosis, and malnutrition. There were many cases of malignant tumors of the digestive system in the patient's family. Genetic testing identified compound heterozygous mutations (c.491+1G>A; c.352_353ins CACC) in epithelial cell adhesion molecule (EpCAM) gene and the patient was hence diagnosed with congenital tufting enteropathy. The patient was given partial parenteral nutrition support. The patient's diarrheal symptom was improved, but it was difficult to increase the amount of formula because any increase in the amount of formula for the patient would inevitably result in abdominal distention and vomiting. The patient experienced repeated fever in the later period of hospitalization and was eventually discharged from the hospital with the family's signed consent. He still had diarrhea and vomiting after leaving the hospital. Four weeks after discharge, the patient lost about 1 kg of weight and eventually died.

Background sensitivity to chemotherapy-induced nausea and vomiting and response to antiemetics in paediatric patients: a genetic association study.

Chemotherapy-induced nausea and vomiting (CINV) remains a common adverse effect for children with cancer. In children, chemotherapy emetogenicity and patient factors such as susceptibility to motion sickness and age group determine a patient's risk of CINV. Besides known risk factors, genetic factors may play a role in interindividual variation in the occurrence of CINV. We investigated the influence of candidate gene polymorphisms on the efficacy of antiemetics and on the background sensitivity to CINV in children. This prospective study included 100 children with cancer (median age 6.4 years, range 0.8-17.9) who received moderately to highly emetogenic chemotherapy. Participants registered nausea and vomiting episodes in a mobile app. Genotypes were determined by whole-genome sequencing (n = 79) or Sanger sequencing (n = 21) for 71 genetic polymorphisms involved in motion sickness and antiemetic pathways. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations between acute CINV and genotypes adjusting for susceptibility to motion sickness and age group. Rs3782025 in the 5-hydroxytryptamine type 3 (5-HT3) receptor gene (HTR3B) [minor allele frequency (MAF): 0.48] affected response to 5-HT3 receptor antagonists; acute CINV occurred in 76% of patients with GA/AA genotypes and in 41% of patients with GG genotype (OR 5.59; 95% CI 1.74-17.9, dominant genetic model). Rs2975226 in the dopamine transporter gene (SLC6A3) (MAF: 0.54) was associated with acute CINV (OR 5.79; 95% CI 1.09-30.67, recessive genetic model). Polymorphisms in HTR3B and SLC6A3 may contribute to the variability in response to antiemetic prophylaxis for CINV in children.

Aldosterone synthase (CYP11B2) deficiency among Palestinian infants: Three novel variants and genetic heterogeneity.

Aldosterone synthase deficiency (ASD) is a rare potentially life-threatening genetic disorder that usually presents during infancy due to pathogenic variants in the CYP11B2 gene. Knowledge about CYP11B2 variants in the Arab population is scarce. Here, we present and analyze five Palestinian patients and their different novel pathogenic variants. Data on clinical presentation, electrolytes, plasma renin activity, and steroid hormone levels of five patients diagnosed with ASD were summarized. Sequencing of the CYP11B2 gene exons was followed by evolutionary conservation analysis and structural modeling of the variants. All patients were from highly consanguineous Palestinian families. The patients presented at 1-4 months of age with recurrent vomiting, poor weight gain, hyponatremia, hyperkalemia, and low aldosterone levels. Genetic analysis of the CYP11B2 gene revealed three homozygous pathogenic variants: p.Ser344Profs*9, p.G452W in two patients from an extended family, and p.Q338stop. A previously described pathogenic variant was found in one patient: p.G288S. We described four different CYP11B2 gene pathogenic variants in a relatively small population. Our findings may contribute to the future early diagnosis and therapy for patients with ASD among Arab patients who present with failure to thrive and compatible electrolyte disturbances.

Acute liver dysfunction with delayed peak of serum aminotransferase levels as a presentation of ornithine transcarbamylase deficiency in females.

We describe 10 females with ornithine transcarbamylase (OTC) deficiency and liver dysfunction, revealing a unique pattern of hepatocyte injury in which initial hyperammonemia and coagulopathy is followed by a delayed peak in aminotransferase levels. None of the patients required urgent liver transplantation, though five eventually underwent transplant for recurrent metabolic crises. We intend that this novel observation will initiate further investigations into the pathophysiology of liver dysfunction in OTC-deficient patients, and ultimately lead to the development of therapies and prevent the need for liver transplant.

Does greater morning sickness predict carrying a girl? Analysis of nausea and vomiting during pregnancy from retrospective report.

PURPOSE: The prevalence of severe nausea and vomiting during pregnancy (NVP) requiring hospitalization has been associated with female fetal sex. However, the question of whether fetal sex and less severe forms of NVP share that association has not been investigated. The objective of this study was to evaluate the relationship between fetal sex and the frequency of NVP. METHODS: We collected self-reported data from mothers via an international web-based survey on the Amazon Mechanical Turk (MTurk) platform about pregnancy and first trimester NVP history. We considered the covariables of maternal age, parity status, proneness to nausea, geographic cohort, and preconceived notions of a relationship between fetal sex and NVP. RESULTS: Two-thousand five hundred and forty-three mothers met the inclusion criteria, yielding data from 4320 pregnancies. Women gestating a female fetus reported higher frequencies of NVP (M = 6.35 on a 1-9 scale) than did women gestating males (M = 6.04, p = .007). This effect held true when all other variables were included in the regression. General proneness to nausea, maternal age, and parity were also significant independent predictors of NVP. CONCLUSIONS: Women that carried a female fetus, as opposed to a male fetus, reported significantly higher frequency of NVP during the first trimester of pregnancy. Further research should evaluate both the proximate and ultimate causes of this relationship.

Analysis of pharmacogenomic factors for chemotherapy-induced nausea and vomiting in patients with breast cancer receiving doxorubicin and cyclophosphamide chemotherapy.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) can lead to a significant deterioration in the quality of life of cancer patients receiving chemotherapy. This study aimed to determine whether ABCB1 2677G > T/A was associated with complete response (CR; defined as no vomiting and no rescue medication) in acute phase (CR0-24), as well as to explore the genetic factors affecting delayed phase (CR24-120) CINV in cancer patients treated with a standard triple antiemetic regimen that included aprepitant. METHODS: This prospective single-center study included a total of 166 chemotherapy-naïve patients with breast cancer who received a standard dose of doxorubicin and cyclophosphamide combination chemotherapy; granisetron, dexamethasone, and aprepitant were administered prior to chemotherapy. CR0-24 was compared between minor allele homozygous (TT, AA, and TA) and major allele homozygous plus heterozygous (GG, GA, and GT) groups of ABCB1 2677G > T/A. In addition, 14 genetic polymorphisms were genotyped and their associations with CRs were investigated. RESULTS: The proportion of patients who achieved CR0-24, which was the primary endpoint of this study, was 59% in the minor allele homozygous and 61% in the major allele homozygous plus heterozygous groups of ABCB1 2677G > T/A. Although this difference was not statistically significant, multivariate logistic regression analysis adjusted for potential risk factors showed that TACR1 1323TT (OR, 2.57; P = 0.014) was a significant determinant of CR24-120. CONCLUSION: No significant association was found between ABCB1 2677G > T/A and CR0-24. However, it was observed that the polymorphism of TACR1, which encodes the neurokinin 1 receptor, might be a potential genetic risk factor for the development of delayed phase CINV.

DGAT1 mutations leading to delayed chronic diarrhoea: a case report.

BACKGROUND: Early-onset chronic diarrhoea often indicates a congenital disorder. Mutation in diacylglycerol o-acyltransferase 1 (DGAT1) has recently been linked to early-onset chronic diarrhoea. To date, only a few cases of DGAT1 deficiency have been reported. Diarrhoea in those cases was severe and developed in the neonatal period or within 2 months after birth. CASE PRESENTATION: Here, we report a female patient with DGAT1 mutations with delayed-onset chronic diarrhoea. The patient had vomiting, hypoalbuminemia, hypertriglyceridemia, and failure to thrive at early infancy. Her intractable chronic diarrhoea occurred until she was 8 months of age. A compound heterozygous DGAT1 mutation was found in the patient, which was first found in the Chinese population. Her symptoms and nutrition status improved after nutritional therapy, including a fat restriction diet. CONCLUSIONS: This case expanded our knowledge of the clinical features of patients with DGAT1 mutations. Intractable diarrhoea with delayed onset could also be a congenital disorder.

Pharmacogenetics of antiemetics for chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

A substantial proportion of cancer patients experience chemotherapy-induced nausea and vomiting (CINV) despite the use of antiemetic drugs. Prevalent genetic polymorphisms involved in antiemetic drug metabolism, drug transport and receptor pathways likely affect the effectiveness of antiemetics. Knowledge on which polymorphisms to integrate into individualised clinical care is needed. We did a systematic review evaluating the association between polymorphisms and effectiveness of antiemetics in cancer patients receiving moderately to highly emetogenic chemotherapy. Twenty studies n = 2331 evaluated eight polymorphisms in five candidate genes involved in 5-HT3 antagonist pathways. HTR3C C1214G increased the risk of acute chemotherapy-induced vomiting in the dominant model (odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.08-6.63). ABCB1 C3435T reduced the risk of acute CINV in the recessive model (OR = 0.60, 95 % CI: 0.44-0.81). Future studies should evaluate candidate genes that affect pharmacogenetics of other antiemetics beside 5-HT3 antagonists.

Identification of genetic polymorphisms modulating nausea and vomiting in two series of opioid-treated cancer patients.

Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in AIM1L, CLCC1, MUC16, PDE3A, POM121L2, and ZNF165 genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in ZNF568 and PDE3A genes. Only one SNP, rs12305038 in PDE3A, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.

Cost-minimization analysis of GSTP1c.313A>G genotyping for the prevention of cisplatin-induced nausea and vomiting: A Bayesian inference approach.

BACKGROUND: Chemotherapy-induced nausea and vomiting are concerning adverse events resulting from cancer treatment, and current guidelines recommend the use of neurokinin-1-selective antagonists, such as fosaprepitant, in highly emetogenic schemes. However, the implementation of this strategy may be limited by the cost of treatment. GSTP1 c.313A>G genotype was recently described as a predictor of vomiting related to high-dose cisplatin. We hypothesized that the inclusion of routine GSTP1 c.313A>G screening may be promising in financial terms, in contrast to the wide-spread use of fosaprepitant. METHODS: A cost-minimization analysis was planned to compare GSTP1 c.313A>G genotyping versus overall fosaprepitant implementation for patients with head and neck cancer under chemoradiation therapy with high-dose cisplatin. A decision analytic tree was designed, and conditional probabilities were calculated under Markov chain Monte Carlo simulations using the Metropolis-Hastings algorithm. The observed data included patients under treatment without fosaprepitant, while priors were derived from published studies. RESULTS: To introduce screening with real-time polymerase chain reaction, an initial investment of U$ 39,379.97 would be required, with an amortization cost of U$ 7,272.97 per year. The mean cost of standard therapy with fosaprepitant is U$ 243.24 per patient, and although the initial cost of routine genotyping is higher, there is a tendency of progressive minimization at a threshold of 155 patients (Credible interval-CI: 119 to 216), provided more than one sample is incorporated for simultaneous analysis. A resulting reduction of 35.83% (CI: 30.31 to 41.74%) in fosaprepitant expenditures is then expected with the implementation of GSTP1 c.313A>G genotyping. CONCLUSION: GSTP1 c.313A>G genotyping may reduce the use of preventive support for chemotherapy induced nausea and lower the overall cost of treatment. Despite the results of this simulation, randomized, interventional studies are required to control for known and unknown confounders as well as unexpected expenses.

Children with cyclic vomiting syndrome: phenotypes, disease burden and mitochondrial DNA analysis.

BACKGROUND: Cyclic vomiting syndrome (CVS) is characterized by repeated, stereotypical vomiting episodes. It is possibly associated with mitochondrial DNA (mtDNA) variants. We examined the phenotype, disease burden, treatment and performed mtDNA analysis in pediatric CVS. METHODS: This retrospective study included 42 children with CVS in a tertiary care center. Information regarding medical history, clinical features, laboratory tests, and treatment were collected. mtDNA sequencing was performed among 13 patients. RESULTS: Mean age of onset among patients was 4.0±3.4 years, and mean age at diagnosis was 6.7±4.2 years. CVS episodes in onset and features were stereotypic. Recognizable prodromes were reported in 54.8% patients. Neuroimaging showed previously unknown intracranial abnormalities. Gastrointestinal infection was found in four patients. Mean duration of hospitalization was 7.0±2.4 days, and mean hospitalization cost was 10,891 RMB. Sequencing showed that 4/13 patients had C16519T mtDNA polymorphism, and 2/13 patients had G3010A mtDNA polymorphism. CONCLUSIONS: Cyclic vomiting syndrome is a disabling disorder, which causes huge disease burdens to the patients and their families. Early clinical suspicion and prompt diagnosis are crucial. mtDNA polymorphisms were found in some patients, but they were not significantly associated with pediatric CVS.

Optimal prophylaxis of chemotherapy-induced nausea and vomiting for moderately emetogenic chemotherapy: a meta-analysis.

AIM: We compare neurokinin-1 receptor antagonist (NK-1RA)-based triple regimen and conventional duplex regimen for antiemetic efficacy for patients with moderately emetogenic chemotherapy (MEC). Patients & methods: Pooled risk ratios (RRs) were used to evaluate the complete response and no significant nausea. The results were separately analyzed for pure MEC regimens, carboplatin-based regimens and oxaliplatin-based regimens. RESULTS: Ten trials focused on MEC involving 2928 cancer patients using NK-1RA triple regimens or conventional duplex regimen were included. NK-1RA-based triple regimen showed significant better complete responses in overall (RR: 1.14; 95% CI: 1.05-1.24), acute (RR: 1.02; 95% CI: 1.00-1.04) and delayed (RR: 1.13; 95% CI: 1.04-1.23) phase compared with duplex regimen in patients with MEC. Similar results were found for no significant nausea. Subgroup analyses showed that triple regimen showed superior antiemetic efficacy significantly in patients with carboplatin-based chemotherapy, instead of oxaliplatin-based chemotherapy. CONCLUSION: NK-1RA is recommended to use in carboplatin-based chemotherapy, not oxaliplatin-based chemotherapy.

Novel fructose bisphosphatase 1 gene mutation presenting as recurrent episodes of vomiting in an Indian child.

Fructose-1, 6-bisphosphatase 1 (FBP1) deficiency is an autosomal recessive disorder of gluconeogenesis resulting in severe and recurrent life-threatening episodes of hypoglycemia and lactic acidosis in infancy. We report a 16 month-old girl who presented with recurrent episodes of vomiting, rapid breathing, lactic acidosis, hyperuricemia, and hypertriglyceridemia. Genetic analysis revealed a novel compound heterozygous mutation in FBP1 gene confirming the diagnosis of FBP1 deficiency. The patient was managed with treatment of acute episodes and preventive long-term dietary modifications. Long-term prognosis of FBP1 deficiency is excellent underlining the importance of early recognition of clinical signs, prompt diagnosis, and avoidance of fasting in this disease. FBP1 gene mutations have been described from various ethnic backgrounds, but there is limited data available from Indian population, hence the importance of this case.

Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum.

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3-2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p < 5 × 10-8) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.