Duffy blood system and g6pd genetic variants in p. Vivax malaria patients from manaus, amazonas, brazil

Abstract Background Over a third of the world’s population lives at risk of potentially severe Plasmodium vivax induced malaria. The unique aspect of the parasite’s biology and interactions with the human host make it harder to control and eliminate the disease. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and Duffy-negative blood groups are two red blood cell variations shown to confer protection against malaria. Methods Molecular genotyping of G6PD and Duffy was performed in 225 patients with severe and non-severe malaria randomly admitted at a reference center for infectious disease from Manaus. For G6PD variants characterization of the variants, Real Time PCR (qPCR) was performed, while Duffy genotyping by PCR-RFLP. Results Of the 225 patients, 29 (12.94%) and 43 (19.19%) were carriers of the G6PD c.202G > A and c.376A > G, respectively. For the Duffy genotype (c.-67T > C in the GATA promoter region), 70 (31.11%) were phenotyped as Fy(a + b-), 98 (43.55%) Fy(a + b+), 56 (24.9%) Fy(a-b+) and 1 (0.44%) Fy(a-b-). The FY*01/FY*02 genotype was prevalent in both non-severe and severe malaria. In women, the FY*01/FY*02 allele occurred concomitantly with c.376A > G more frequently in non-severe malaria, while in men, this combination was predominant in severe malaria. Duffy phenotype Fy(a-b+) (p = 0.022) and genotypes FY*01/FY*01 / FY*02/FY*02 (p = 0.015) correlated with high parasitemia density before and after treatment. Conclusions Our results showed only one uncomplicated vivax malaria patient with Duffy phenotype Fy(a-b-). Heterozygous GATA variants did not confer protection against malaria infection in this study. Research on G6PD and Duffy antigen deficiencies has been valuable, particularly when focused on densely populated areas. Our results confirm possible genetic molding mechanisms in vivax malaria in our Amazon region and can help to improve the understanding of the relationship between G6PD deficiency and Duffy genotypes concomitantly in the protection or susceptibility to P. vivax infection. Molecular diagnosis before treatment may be necessary in the Amazonian population, regardless of the diagnosis of uncomplicated or severe malaria.

Download Full-text

Duffy Blood System and G6PD Genetic Variants In P. Vivax Malaria Patients From Manaus, Amazonas, Brazil

10.21203/rs.3.rs-41862/v3 ◽

2020 ◽

Author(s):

Natália Santos Ferreira ◽

Jéssica Lorena dos Santos Mathias ◽

Sérgio Roberto Lopes Albuquerque ◽

Anne Cristine Gomes Almeida ◽

Ana Carla Dantas ◽

...

Keyword(s):

Severe Malaria ◽

Genetic Variants ◽

Vivax Malaria ◽

Promoter Region ◽

Blood System ◽

Duffy Antigen ◽

Unique Aspect ◽

Genotype C ◽

Glucose 6 Phosphate Dehydrogenase ◽

Duffy Negative

Abstract Over a third of the world’s population lives at risk of potentially severe Plasmodium vivax induced malaria. The unique aspect of the parasite’s biology and interactions with the human host make it harder to control and eliminate the disease. Glucose-6-phosphate dehydrogenase (G6PD) deficiency and Duffy-negative blood groups are two red blood cell variations that confer protection against malaria. Molecular genotyping of G6PD and Duffy was performed in 225 patients with severe and non-severe malaria. Of the 225 patients, 29 (12.94%) and 43 (19.19%) were carriers of the G6PD c.202G>A and c.376A>G, respectively. For the Duffy genotype (c.-67T>C in the GATA promoter region), 70 (31.11%) were phenotyped as Fy(a+b-), 98 (43.55%) Fy(a+b+), 56 (24.9%) Fy(a-b+) and 1 (0.44%) Fy(a-b-). The FY*01/FY*02 genotype was prevalent in both non-severe and severe malaria. However, the frequency increased when SNP c.376A>G was also present. In women, the FY*01/FY*02 allele occurred concomitantly with c.376A>G more frequently in non-severe malaria, while in men, this combination is revealed predominantly in severe malaria. G202A and A376G G6PD variants were higher in severe malaria, with c.202G>A (RR= 4.76 – p=.009) and c.376A>G (RR: 6.47 – p<0.001) strongly associated with the trials malaria (p<0.001). Duffy phenotype Fy(a-b+) (p=0.003) and genotype FY*02/ FY*02 (p=0.007) presented the highest values parasitemia density of the vivax malaria. Research on G6PD and Duffy antigen deficiencies has been valuable, particularly when focused on densely populated areas. Altogether, c.202G>A and c.376A>G SNPs seem to be risk factors for the development of severe vivax malaria. Molecular diagnosis before treatment may be necessary in the Amazonian population and uncomplicated malaria showed a greater frequency of variation for GATA and G6PD variants than severe malaria.

Download Full-text

Fine mapping of Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency in rural area of South West Odisha using the clinical, hematological and molecular approach

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2020.015 ◽

2020 ◽

Vol 12 (1) ◽

pp. e2020015

Author(s):

Ravindra Kumar ◽

MPSS Singh ◽

Soumendu Mahapatra ◽

Sonam Chourasia ◽

Malay Kumar Tripathi ◽

...

Keyword(s):

G6pd Deficiency ◽

Clinical History ◽

South West ◽

Normal Individuals ◽

Pcr Rflp ◽

History Of ◽

Tribal Populations ◽

Glucose 6 Phosphate Dehydrogenase ◽

National Prevalence

Introduction: The aim of the study was to enumerate the clinical, hematological and molecular spectrum of G6PD deficiency in malaria endemic regions of south west Odisha. Methods: Diagnosis of G6PD deficiency was made by using the Di-chloroindophenol Dye test in from two south west districts (Kalahandi and Rayagada) of Odisha State. Demographic and clinical history was taken from each individual using a pre-structured questionnaire. Molecular characterization of G6PD deficiency was done using PCR-RFLP and Sanger sequencing. Results: A total of 1981 individuals were screened, out of which 59 (2.97%) individuals were found G6PD deficient. Analysis revealed that G6PD deficiency was more in males (4.0%) as compared to females (2.3%). G6PD deficiency was significantly higher in tribal population (4.8%) as compared to non-tribal populations (2.4%) (p=0.012, OR=2.014, 95%CI =1.206-3.365). Individuals with history of malaria and G6PD deficiency have high risk of need of blood transfusion than G6PD normal individuals (p=0.026, OR=3.816, 95%CI=1.079-13.496). Molecular analysis revealed G6PD Orissa as the most common (88%) mutation 88% in the studied cohort. G6PD Kaiping (n=3), G6PD Coimbra (n=2) and G6PD Union (n=1) were also identified in studied cohort. Conclusion: The cumulative prevalence of G6PD deficiency the present is below the estimated national prevalence. G6PD deficiency was higher in tribes as compared to non-tribes. Rare G6PD Kaiping and G6PD Union variants have been identified.

Download Full-text

Duffy Blood System and G6PD Genetic Variants In P. Vivax Malaria Patients From Manaus, Amazonas, Brazil

10.21203/rs.3.rs-41862/v2 ◽

2020 ◽

Author(s):

Natália Santos Ferreira ◽

Jéssica Lorena dos Santos Mathias ◽

Sérgio Roberto Lopes Albuquerque ◽

Anne Cristine Gomes Almeida ◽

Ana Carla Dantas ◽

...

Keyword(s):

Severe Malaria ◽

Genetic Variants ◽

Vivax Malaria ◽

Promoter Region ◽

Blood System ◽

Duffy Antigen ◽

Unique Aspect ◽

Genotype C ◽

Glucose 6 Phosphate Dehydrogenase ◽

Duffy Negative

Download Full-text

Molecular Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in the Shenzhen Population

Human Heredity ◽

10.1159/000516808 ◽

2021 ◽

pp. 1-7

Author(s):

Jian Gao ◽

Sheng Lin ◽

Shiguo Chen ◽

Qunyan Wu ◽

Kaifeng Zheng ◽

...

Keyword(s):

G6pd Deficiency ◽

Amplification Refractory Mutation System ◽

Gene Variants ◽

Coding Region ◽

G6pd Gene ◽

Mutation System ◽

Hotspot Mutations ◽

Glucose 6 Phosphate Dehydrogenase ◽

Generation Sequencing

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. This study aimed to characterize the G6PD gene variant distribution in Shenzhen of Guangdong province. Methods: A total of 33,562 individuals were selected at the hospital for retrospective analysis, of which 1,213 cases with enzymatic activity-confirmed G6PD deficiency were screened for G6PD gene variants. Amplification refractory mutation system PCR was first used to screen the 6 dominant mutants in the Chinese population (c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, c.392G>T, and c.871G>A). If the 6 hotspot variants were not found, next-generation sequencing was then performed. Finally, Sanger sequencing was used to verify all the mutations. Results: The incidence of G6PD deficiency in this study was 3.54%. A total of 26 kinds of mutants were found in the coding region, except for c.-8-624T>C, which was in the noncoding region. c.1376G>T and c.1388G>A, both located in exon 12, were the top 2 mutants, accounting for 68.43% of all individuals. The 6 hotspot mutations had a cumulative proportion of 94.02%. Conclusions: This study provided detailed characteristics of G6PD gene variants in Shenzhen, and the results would be valuable to enrich the knowledge of G6PD deficiency.

Download Full-text

Characterization of the relationship between olfactory perception and the release of aroma compounds before and after simulated oral processing

Journal of Dairy Science ◽

10.3168/jds.2020-19026 ◽

2021 ◽

Author(s):

Shuo Mu ◽

Lu Liu ◽

Hongna Liu ◽

Qingwu Shen ◽

Jie Luo

Keyword(s):

Aroma Compounds ◽

Olfactory Perception ◽

Before And After ◽

Oral Processing ◽

The Relationship

Download Full-text

Protective effect of Mediterranean-type glucose-6-phosphate dehydrogenase deficiency against Plasmodium vivax malaria

eLife ◽

10.7554/elife.62448 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ghulam R Awab ◽

Fahima Aaram ◽

Natsuda Jamornthanyawat ◽

Kanokon Suwannasin ◽

Watcharee Pagornrat ◽

...

Keyword(s):

Protective Effect ◽

Plasmodium Vivax ◽

G6pd Deficiency ◽

Vivax Malaria ◽

Malaria Incidence ◽

Large Population ◽

Credible Interval ◽

Radical Cure ◽

Plasmodium Vivax Malaria ◽

Glucose 6 Phosphate Dehydrogenase

X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzymopathy. The severe Mediterranean variant (G6PD Med) found across Europe and Asia is thought to confer protection against malaria, but its effect is unclear. We fitted a Bayesian statistical model to observed G6PD Med allele frequencies in 999 Pashtun patients presenting with acute Plasmodium vivax malaria and 1408 population controls. G6PD Med was associated with reductions in symptomatic P. vivax malaria incidence of 76% (95% credible interval [CI], 58–88) in hemizygous males and homozygous females combined and 55% (95% CI, 38–68) in heterozygous females. Unless there is very large population stratification within the Pashtun (confounding these results), the G6PD Med genotype confers a very large and gene-dose proportional protective effect against acute vivax malaria. The proportion of patients with vivax malaria at risk of haemolysis following 8-aminoquinoline radical cure is substantially overestimated by studies measuring G6PD deficiency prevalence in healthy subjects.

Download Full-text

Prevalence and Genetic Characterization of Glucose-6-Phosphate Dehydrogenase Deficiency in Anemic Subjects from Uttar Pradesh, India

Journal of Pediatric Genetics ◽

10.1055/s-0039-1677729 ◽

2019 ◽

Vol 08 (02) ◽

pp. 047-053 ◽

Cited By ~ 1

Author(s):

Poonam Tripathi ◽

Sarita Agarwal ◽

Srinivasan Muthuswamy

Keyword(s):

G6pd Deficiency ◽

Dehydrogenase Deficiency ◽

Genetic Characterization ◽

Gene Mutations ◽

Uttar Pradesh ◽

Chromosome X ◽

G6pd Gene ◽

Glucose 6 Phosphate Dehydrogenase ◽

Fluorescent Spot

AbstractGlucose-6-phosphate dehydrogenase (G6PD) deficiency is caused by one or more mutations in the G6PD gene on chromosome X. It affects approximately 400 million people worldwide. The purpose of this study was to detect the prevalence of G6PD deficiency and G6PD gene mutations in the hospital-based settings in patients referred for suspected G6PD deficiency. A qualitative fluorescent spot test and dichlorophenol-indolphenol (DCIP) test were performed. G6PD-deficient, positive samples were further processed for mutation analysis by Sanger sequencing. Out of 1,069 cases, 95 (8.8%) were detected as G6PD deficient (by DCIP test) and were sent for molecular analysis. The G6PD Mediterranean mutation (563C > T) is the most common variant among G6PD-deficient individuals followed by the Coimbra (592C→T) and Orissa (131C→G) variants. We concluded that all symptomatic patients (anemic or jaundiced) should be investigated for G6PD deficiency. Our findings will inform our population screening approach and help provide better management for G6PD-deficient patients.

Download Full-text

Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in patients of Chinese descent and identification of new base substitutions in the human G6PD gene

Blood ◽

10.1182/blood.v81.8.2150.2150 ◽

1993 ◽

Vol 81 (8) ◽

pp. 2150-2154 ◽

Cited By ~ 40

Author(s):

DT Chiu ◽

L Zuo ◽

L Chao ◽

E Chen ◽

E Louie ◽

...

Keyword(s):

G6pd Deficiency ◽

Point Mutations ◽

Nucleotide Substitutions ◽

New Findings ◽

G6pd Gene ◽

High Prevalence ◽

Chinese Descent ◽

Glucose 6 Phosphate Dehydrogenase ◽

Sequencing Procedure

Abstract The underlying DNA changes associated with glucose-6-phosphate dehydrogenase (G6PD)-deficient Asians have not been extensively investigated. To fill this gap, we sequenced the G6PD gene of 43 G6PD- deficient Chinese whose G6PD was well characterized biochemically. DNA samples were obtained from peripheral blood of these individuals for sequencing using a direct polymerase chain reaction (PCR) sequencing procedure. From these 43 samples, we have identified five different types of nucleotide substitutions in the G6PD gene: at cDNA 1388 from G to A (Arg to His); at cDNA 1376 from G to T (Arg to Leu); at cDNA 1024 from C to T (Leu to Phe); at cDNA 392 from G to T (Gly to Val); at cDNA 95 from A to G (His to Arg). These five nucleotide substitutions account for over 83% of our 43 G6PD-deficient samples and these substitutions have not been reported in non-Asians. The substitutions found at cDNA 392 and cDNA 1024 are new findings. The substitutions at cDNA 1376 and 1388 account for over 50% of the 43 samples examined indicating a high prevalence of these two alleles among G6PD-deficient Chinese. Our findings add support to the notion that diverse point mutations may account largely for much of the phenotypic heterogeneity of G6PD deficiency.

Download Full-text

Molecular characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency by natural and amplification created restriction sites: five mutations account for most G6PD deficiency cases in Taiwan

Blood ◽

10.1182/blood.v80.4.1079.1079 ◽

1992 ◽

Vol 80 (4) ◽

pp. 1079-1082 ◽

Cited By ~ 40

Author(s):

JG Chang ◽

SS Chiou ◽

LI Perng ◽

TC Chen ◽

TC Liu ◽

...

Keyword(s):

G6pd Deficiency ◽

Restriction Enzymes ◽

Common Mutation ◽

Simple Method ◽

Molecular Defects ◽

G6pd Gene ◽

Restriction Sites ◽

Glucose 6 Phosphate Dehydrogenase ◽

Deficiency Cases

Abstract We have developed a rapid and simple method to diagnose the molecular defects of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Chinese in Taiwan. This method involves the selective amplification of a DNA fragment from human G6PD gene with specific oligonucleotide primers followed by digestion with restriction enzymes that recognize artificially created or naturally occurring restriction sites. Ninety- four Chinese males with G6PD deficiency were studied. The results show that 50% (47 of 94) were G to T mutation at nucleotide (nt) 1376, 21.3% (20 of 94) were G to A mutation at nt 1388, 7.4% (7 of 94) were A to G mutation at nt 493, 7.4% (7 of 94) were A to G mutation at nt 95, 4.2% (4 of 94) were C to T mutation at nt 1024, 1.1% (1 of 94) was G to T mutation at nt 392, and 1.1% (1 of 94) was G to A mutation at nt 487. These results show that the former five mutations account for more than 90% of G6PD deficiency cases in Taiwan. Aside from showing that G to T change at nt 1376 is the most common mutation, our research indicates that nt 493 mutation is a frequent mutation among Chinese in Taiwan. We compared G6PD activity among different mutations, without discovering significant differences between them.

Download Full-text

Severe Malaria Complicated by G6PD Deficiency in a Pediatric Tanzanian Immigrant

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-19.4.325 ◽

2014 ◽

Vol 19 (4) ◽

pp. 325-334

Author(s):

Heather N. Damhoff ◽

Robert J. Kuhn ◽

Laura P. Stadler

Keyword(s):

United States ◽

Plasmodium Falciparum ◽

Severe Malaria ◽

G6pd Deficiency ◽

Dehydrogenase Deficiency ◽

Febrile Illness ◽

The United States ◽

The World ◽

Glucose 6 Phosphate Dehydrogenase ◽

Dual Infections

Approximately 1,500 cases of malaria are diagnosed in the United States each year. Most cases are travelers and immigrants returning from parts of the world where malaria transmission occurs. Malaria is the most frequent cause of systemic febrile illness without localizing symptoms in travelers returning from the developing world, so vigilance by providers is needed when evaluating patients returning from areas in which malaria is endemic. Despite the availability of effective treatment, malaria still accounts for more than 1 million deaths per year worldwide, with rates being disproportionately high in young children under the age of 5. We present the case of a 4-year-old refugee who emigrated from Tanzania with severe malaria due to dual infections of Plasmodium falciparum and P. ovale, whose treatment course was complicated by quinidine gluconate cardiotoxicity and glucose-6-phosphate dehydrogenase deficiency.

Download Full-text