Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “G6PD”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed2003

Glucose-6-phosphate dehydrogenase modulates cytosolic redox status and contractile phenotype in adult cardiomyocytes.

Reactive oxygen species (ROS)-mediated cell injury contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. Protection against ROS requires maintenance of endogenous thiol pools, most importantly, reduced glutathione (GSH), by NADPH. In cardiomyocytes, GSH resides in two separate cellular compartments: the mitochondria and cytosol. Although mitochondrial GSH is maintained largely by transhydrogenase and isocitrate dehydrogenase, the mechanisms responsible for sustaining cytosolic GSH remain unclear. Glucose-6-phosphate dehydrogenase (G6PD) functions as the first and rate-limiting enzyme in the pentose phosphate pathway, responsible for the generation of NADPH in a reaction coupled to the de novo production of cellular ribose. We hypothesized that G6PD is required to maintain cytosolic GSH levels and protect against ROS injury in cardiomyocytes. We found that in adult cardiomyocytes, G6PD activity is rapidly increased in response to cellular oxidative stress, with translocation of G6PD to the cell membrane. Furthermore, inhibition of G6PD depletes cytosolic GSH levels and subsequently results in cardiomyocyte contractile dysfunction through dysregulation of calcium homeostasis. Cardiomyocyte dysfunction was reversed through treatment with either a thiol-repleting agent (L-2-oxothiazolidine-4-carboxylic acid) or antioxidant treatment (Eukarion-134), but not with exogenous ribose. Finally, in a murine model of G6PD deficiency, we demonstrate the development of in vivo adverse structural remodeling and impaired contractile function over time. We, therefore, conclude that G6PD is a critical cytosolic antioxidant enzyme, essential for maintenance of cytosolic redox status in adult cardiomyocytes. Deficiency of G6PD may contribute to cardiac dysfunction through increased susceptibility to free radical injury and impairment of intracellular calcium transport. The full text of this article is available online at http://www.circresaha.org.

Animals↗
PubMed2002

Deletion of leucine 61 in glucose-6-phosphate dehydrogenase leads to chronic nonspherocytic anemia, granulocyte dysfunction, and increased susceptibility to infections.

In this study the blood cells of 4 male patients from 2 unrelated families with chronic nonspherocytic anemia and recurrent bacterial infections were investigated. The activity of glucose-6- phosphate dehydrogenase (G6PD) in the red blood cells and in the granulocytes of these patients was below detection level. Moreover, their granulocytes displayed a decreased respiratory burst upon activation. Sequencing of genomic DNA revealed a novel 3-base pair (TCT) deletion in the G6PD gene, predicting the deletion of a leucine at position 61. The mutant G6PD protein was undetectable by Western blotting in the red blood cells and granulocytes of these patients. In phytohemagglutinin-stimulated lymphocytes the G6PD protein was present, but the amount of G6PD protein was strongly diminished in the patients' cells. Purified mutant protein from an Escherichia coli expression system showed decreased heat stability and decreased specific activity. Furthermore, we found that the messenger RNA of G6PD(180-182delTCT) is unstable, which may contribute to the severe G6PD deficiency observed in these patients. We propose the name "G6PD Amsterdam" for this new variant.

Adolescent↗
PubMed1981

Glucose-6-phosphate dehydrogenase red blood cell phenotype in GdMediterranean heterozygous females and hemizygous males at birth.

The distribution of red blood cell G6PD phenotype was studied by means of the methemoglobin elution test in newborn (46) and adult (50) GdMediterranean heterozygous females and newborn (20) and adult (30) hemizygous males. Newborn heterozygotes had a statistically significant (P less than 0.0005) lower mean red blood cell G6PD enzymatic activity (3.23 +/- 1.04) than did normal newborns (8.78 +/- 1.91), whereas there was no significant difference (P greater than 0.30) from the mean of adult heterozygotes (2.93 +/- 0.86). Like adults, newborn heterozygous females showed: (1) a clear correlation (P less than 0.001) between the percentage of enzyme-deficient red blood cells and G6PD enzymatic activity; and (2) the expected two red blood cell population, i.e., one deficient and the other normal (mosaicism). However, in newborns, the distribution of the subjects according to G6PD-deficient red blood cell percentage (mean percent, 43.67) was significantly shifted (P less than 0.025) in favour of the normal phenotype, unlike adult heterozygotes, who showed a symmetrical distribution of G6PD positive and negative red blood cells (mean percent G6PD-deficient red blood cells, 53.27; P greater than 0.20). Newborn hemizygous males showed a consistent percentage (average, 8.28 +/- 2.2) of stained red blood cells due to the presence of young erythrocytes (pseudomosaicism) unlike the occasional stained cells (less than or equal to 5) seen in adults. The prevalence of hyperbilirubinemia in hemizygous males and heterozygous females was 10.22 and 2.2%, respectively, whereas in G6PD normal newborns it was 5.1%. The practical implication of this study is that the diagnosis at birth of the heterozygous state for G6PD deficiency of the Mediterranean type may be more difficult than in adults. Therefore, very sensitive methods, such as the methemoglobin elution test, should be carried out.

Erythrocytes↗
PubMed2001

Overexpression of glucose-6-phosphate dehydrogenase in genetically modified Saccharomyces cerevisiae.

Glucose-6-phosphate dehydrogenase (G6PD) (EC 1.1.1.49) is an abundant enzyme in Saccharomyces cerevisiae. This enzyme is of great interest as an analytical reagent because it is used in a large number of quantitative assays. A strain of S. cerevisiae was genetically modified to improve G6PD production during aerobic culture. The modifications are based on cloning the G6PD sequence under the control of promoters that are upregulated by the carbon source used for yeast growth. The results showed that S. cerevisiae acquired from a commercial source and the same strain produced by aerobic cultivation under controlled conditions provided very similar G6PD. However, G6PD production by genetically modified S. cerevisiae produced very high enzyme activity and showed to be the most effective procedure to obtain glucose-6-phosphate dehydrogenase. As a consequence, the cost of producing G6PD can be significantly reduced by using strains that contain levels of G6PD up to 14-fold higher than the level of G6PD found in commercially available strains.

Aerobiosis↗
PubMed1998

Erythrocyte glucose-6-phosphate dehydrogenase activity assay and affinity for its substrate under "physiological" conditions.

Glucose-6-phosphate dehydrogenase (G6PD) activity and the affinity for its substrate glucose-6-phosphate were investigated under conditions similar to the physiological environment in terms of ionic strength (I: 0.188), cation concentration, pH 7.34, and temperature (37 degrees C). A 12.4, 10.4 and 21.4% decrease was observed in G6PD B, G6PD A+ and G6PD A- activities, respectively. A Km increase of 95.1, 94.4 and 95.4% was observed in G6PD B, G6PD A+ and G6PD A-, respectively, leading to a marked decrease in affinity. In conclusion, the observation of the reduced activity and affinity for its natural substrate reflects the actual pentose pathway rate. It also suggests a much lower NADPH generation, which is crucial mostly in G6PD-deficient individuals, whose NADPH availability is poor.

Blood Physiological Phenomena↗
PubMed1981

The effects of alloxan diabetes, insulin and epinephrine on glucose-6-phosphate dehydrogenase from rat liver and brain.

The control of glucose-6-phosphate dehydrogenase (G6PD) activity of the liver and brain were studied in normal and alloxan diabetic rats. Fasting decreased G6PD activity in brains and livers of normal rats significantly, but these decreases were reversed by placing the rats on a sucrose-rich diet. Injection of insulin were reversed by placing the rats on the sucrose-rich diet. Injection of insulin into normal 48h fasted rats had no significant effect on G6PD activity after 15 min. However, epinephrine significantly decreased liver G6PD activity by 17%, 7.5 min, after injection. Epinephrine had no effect on brain G6PD activity. In fed alloxan diabetic animals, the G6PD activity was found to be about 50% of that found in normal rats. Treatment of diabetic rats with protamine insulin partially reversed the decrease in G6PD activity caused by alloxan diabetes. It is concluded that insulin and epinephrine are important for the regulation of G6PD activity in vivo.

Animals↗
PubMed1987

Superoxide dismutase activity and reduced glutathione content in cataractous lens of patients with glucose-6-phosphate dehydrogenase deficiency.

In the present research we have assayed the glucose-6-phosphate dehydrogenase, superoxide dismutase activities and reduced glutathione content in human cataractous lenses of 83 Sicilian subjects. Five of 45 males were G6PD deficient, whereas eight of 38 females showed a significant reduction in G6PD by 50%. The five males hemizygous for G6PD defect showed undetectable G6PD activity and low GSH levels in their lenses when compared to cataractous patients without erythrocyte G6PD deficiency; on the contrary, the specific activity of lenticular total SOD was found to be significantly increased. The G6PD and SOD activities as well as GSH levels, in the lenses of eight females with intermediate erythrocyte G6PD levels, were not significantly different when compared to females with normal erythrocyte G6PD activity.

Aged↗
PubMedDate not supplied

Correlation between normal glucose-6-phosphate dehydrogenase level and haematological parameters.

The study involved 143 individuals and aimed to correlate normal glucose-6-phosphate dehydrogenase (G6PD) level with haematological parameters. A statistically significant negative correlation was found between G6PD level and haemoglobin, packed cell volume, red blood cell count, mean corpuscular haemoglobin and mean corpuscular volume. A statistically significant positive correlation was found between G6PD level and white blood cell count and reticulocyte count, but no significant correlation was found between G6PD level and mean corpuscular haemoglobin concentration. The negative correlation between G6PD level and haemoglobin suggests that anaemic people have higher G6PD levels than normal individuals. The positive correlation between G6PD level and white blood cell count indicates that white blood cells may play an important role in contributing to G6PD level.

Adolescent↗
PubMed2003

Genetic Blood Disorders Survey in the Sultanate of Oman.

The Genetic Blood Disorders Survey is the first community-based survey in the Arabic world and the Middle East to determine the prevalence of the most common genetic blood disorders. The objective of the survey was to determine the prevalence of the most common genetic blood disorders reported among Omani children under 5 years of age in order to provide the planners and policy-makers with reliable information suitable for formulating health policies, planning, and evaluation. The survey was designed, executed, and financed by the Ministry of Health of the Sultanate of Oman. To reduce costs and save effort and time, data collection for the survey was implemented with the Gulf Family Health Survey (GFHS). The GFHS in the Sultanate of Oman is a research project undertaken by the Council of Health Ministers of the Gulf Co-operation Council States. The six member countries have participated in this GFHS project. A total of 6103 households were interviewed. From these households 6342 children under 5 years of age were taken by their parents to neighbourhood hospitals or health centres for blood collection. Fifty-one per cent of the sample were male and 49 per cent were female. Among the child respondents, 17.9 per cent were in the age group 0 to < 1 year, 20.3 per cent were in the age group 1 to < 2 years, 21.1 per cent were in the age group 2 to < 3 years, 20.5 per cent were in the age group 3 to < 4 years, and 20.2 per cent were in the age group 4 to 5 years. Fifty-five per cent of the mothers of the children studied were illiterate, 9 per cent could read and write but had less than primary education, 20 per cent had completed primary school, 9 per cent had attended preparatory school, 5 per cent had attended secondary school, 1 per cent had had intermediate education, while 0.6 per cent had completed university or higher education. The results of this survey revealed that haemoglobinopathies are prevalent in Oman; the prevalence of sickle cell trait was 6 per cent, and of beta-thalassaemia 2 per cent. The prevalence of sickle cell and homozygous beta-thalassaemia were 0.2 and 0.07 per cent, respectively. Other abnormal haemoglobins (Hb) have been detected in this survey; HbD (0.6 per cent), HbE (0.3 per cent), HbC (0.02 per cent). Combination of sickle cell with other abnormal Hb was also detected at low prevalence. Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency had a high prevalence in Oman, being 25 per cent in males and 10 per cent in females. Among the children studied, three-quarters (74.5 per cent) were found to be free from haemoglobinopathies and G6PD normal, the rest (25.5 per cent), either had haemoglobinopathies (7.5 per cent), G6PD deficiency (16 per cent) or a combination of G6PD deficiency with at least one abnormal Hb (2 per cent). The prevalence of total haemoglobinopathies in Oman was 9.5 per cent. The prevalence of sickle cell trait varied between regions, North Sharqiya had the highest prevalence of 10 per cent. Dakhiliya (9 per cent), followed by Muscat and South Batinah 8 and 7.9 per cent, respectively. The prevalence of sickle cell trait declined by a half in Musandam, South Sharqiya, Dhahira, and North Batinah (4.7, 3.9, 3.9, and 2.9 per cent respectively). Dhofar had the lowest prevalence of 0.2 per cent and no cases of sickle cell trait were found in the Al-Wousta region in the sample selected. The prevalence of beta-thalassaemia trait ranged from 3.9 to 0.2 per cent. Three regions had high rates: North Batinah (3.9 per cent), Muscat (2.8 per cent), and Dakhiliya (2 per cent). The other five regions in the Sultanate have lower rates: Dhahira (1.7 per cent), Musandam (1.6 per cent), South Batinah (1.5 per cent), South Sharqiya (1.2 per cent), and North Sharqiya (1.1 per cent). The prevalence of beta-thalassaemia trait in Dhofar was 0.2 per cent and no cases were detected in the Al-Wousta region. The prevalence of G6PD deficiency reached 29 per cent in Dakhiliya, 26 per cent in South Batinah, 21 per cent in Dhahira, 19 per cent in Muscat and 17 per cent in North Sharqiya and North Batinah. The prevalence declined to 10 per cent in Musandam, 9 per cent in South Sharqiya, Dhofar had the lowest prevalence of 2 per cent and no cases of G6PD deficiency were found in Al-Wousta. The male to female ratio was 2.5:1. In all regions of the Sultanate, prevalence of G6PD deficiency in males were more than twice those in females. From the above rates, it could be calculated that in the whole Sultanate 44,733 children under 5 years of age have G6PD deficiency, 14,306 have sickle cell trait, 474 have sickle cell disease, 5393 have beta-thalassaemia trait, and 175 have beta-thalassaemia major. The study showed that the mean Hb level of children under 5 years of age was 10.9 g/dl for both males and females; the mean Hb level for males was 10.89 g/dl and for females 10.99 g/dl, the difference between males and females was significant. The study revealed that half of the children under 5 years of age were anaemic. Mild anaemia was predominant (46 per cent), while moderate and severe anaemia were 4 and 0.2 per cent respectively. The status of anaemia among children improved with age; mild anaemia was prevalent in 65 per cent of children between ages 0 to < or = 1 years then decreased with age until it reached 30 per cent at 4-5 years of age. The survey produced the first normal haematological indices for children under 5 years of age to be used as a reference in the country. The blood picture of the normal subjects in the survey showed that the mean Hb value for males was 11.9 g/dl and for females 11.8 g/dl. The children had reduced values of MCH and MCV compared to normal international values, the reason for this could be alpha-thalassaemia or iron deficiency. The children maintained high values of HbF (more than 1.2 per cent) even after their first birthday. HbF reached its normal level at 5 years of age. Marriage of first cousins among the parents of the children studied under 5 years of age was 34 per cent. Total consanguinity rate including second cousin relationships and beyond was 58 per cent. We recommend that a national prevention programme for genetic blood disorders be formulated by the authorities. The programme could be included in the Ministry of Health 5-year health development programme for prevention of non-communicable diseases which already exists.

Anemia, Sickle Cell↗
PubMed2003

Quality assurance program for neonatal screening of glucose-6-phosphate dehydrogenase deficiency.

The nationwide neonatal screening of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Taiwan was started on July 1, 1987. The effective collection rate has reached more than 96% of all newborns since 1993 and the overall incidence rate of G6PD deficiency was about 2%. This screening program has 3 screening centers and 18 referral hospitals, distributed around Taiwan including outlying islands. To assess the reliability of the confirmatory and screening tests, an external quality assurance (QA) program for G6PD assay was developed. For quantitative assay of G6PD activity, lyophilized quality control materials with different G6PD activities were prepared from red blood cells. For G6PD screening, quality control materials with different G6PD activities were prepared from whole blood and spotted onto the blood collecting filter paper. Periodically (1-2 months), the QC materials were sent to each of the referral hospitals and screening centers by speed post delivery. The external QA results were evaluated and compared to the median of all the reports and the reference values determined by our laboratory. Whenever an analytical system error was detected in any participating laboratory, troubleshooting was carried out either by contacting by phone or visiting in person. Twenty-one referral laboratories and 8 screening centers (3 in Taiwan, 2 in Mainland China, and one each in the Philippines, Thailand and Lebanon) participated in the QA program. Three to 5 QC specimens were sent to every participating referral laboratory for each quantitative survey. From January 1988 to June 2001, 104 QA surveys were carried out and 1,891 reports were received. Two hundred and thirty-nine (12.6%, 239/1,891) QA reports had abnormal results, attributed to clerical (13%, 31/239), experimental (17.2%, 41/239), and instrumental errors (46.4%, 111/239). Most of the experimental and instrumental errors were found in those laboratories that did not execute internal QA properly. For the screening QA program, 10 QC blood spots were delivered to every participating screening center for each survey. From March 1999 to June 2001, 15 screening surveys were performed with 111 reports received. One false negative (1/1,110) and 14 (14/1,110) false positive results were found in four (3.6%, 4/111) of the screening QA reports. The external quality assurance program proved useful for monitoring the performance of G6PD tests in referral hospitals and screening centers, and provided guidance for correcting analytical errors.

Blood Specimen Collection↗
PubMed1988

RFLP of the X chromosome-linked glucose-6-phosphate dehydrogenase locus in blacks.

The X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD) A(+) variant is found in approximately 20% of blacks. Examination of the structure of the G6PD A(+) gene revealed that AT----GC transition occurred in the variant gene, resulting in the amino acid substitution Asn----Asp at the one hundred forty-second position from the NH2-terminal of the enzyme (Takizawa and Yoshida 1987). The nucleotide change created an additional FokI cleavage site in the variant A(+) gene; thus, the FokI fragment type of the variant A(+) DNA differs from that of the normal B(+) DNA. PvuII fragment type is also found to be polymorphic in blacks, but not in Caucasians. The majority of blacks, as well all nonblacks, have a major hybridization-positive fragment of approximately 4.0 kbp (PvuII type 1), while approximately 20% of blacks have a major fragment of approximately 1.5 kbp (PvuII type 2). The G6PD gene with PvuII type 2 contains an additional PvuII cleavage site approximately 0.7 kbp downstream from the mutation site of the G6PD A(+). Approximately 40% of the G6PD A(+) genes have PvuII type 2, while only approximately 10% of the G6PD B(+) genes are associated with PvuII type 2. The data indicate a statistically significant (X2 = 6.85, P less than .020) linkage disequilibrium between the G6PD types and the PvuII types at the G6PD locus.

Black People↗
PubMed1984

Partial purification and characterization of the messenger RNA for human glucose-6-phosphate dehydrogenase.

Glucose-6-phosphate dehydrogenase (G6PD) is a household enzyme that accounts, in many cells, for about 0.03% of cellular protein. We have developed an assay for G6PD-specific mRNA based on in vitro translation of RNA from human fibroblasts and immunoprecipitation of the translation products with an anti-G6PD antiserum. By making use of this assay, G6PD mRNA has been purified 50 to 100-fold in three steps. We estimate that the mRNA encoding G6PD constitutes less than 0.02% of total poly(A)+ RNA in human fibroblasts. The size of the G6PD mRNA has been established in denaturing conditions as being in the range between 2800 and 3200 nucleotides. This has been confirmed by Northern blot analysis. Since the G6PD coding sequence is estimated to be about 1491 nucleotides, the G6PD mRNA has long untranslated sequences, most of which is at the 3' end and which may be heterogeneous in length. The sequence of the last 608 nucleotides of this mRNA has been determined.

Cells, Cultured↗
PubMed1984

[Microsomal glucose 6-phosphate dehydrogenase in the rat testis--an testis--specific isoenzyme?].

Mammalian tissues contain cytosolic and microsomal glucose 6-phosphate dehydrogenase (G6PD). In the present study it was examined whether the microsomal G6PD in liver and testis of the rat are homologous. Kinetic parameters and immunological reactivity were estimated using rabbit antiserum against mice erythrocyte G6PD. Kinetic parameters allow to distinguish cytosolic and microsomal G6PD in rat liver but not in testis, whereas the immunological properties of the testis enzymes are different. The cytosolic G6PDs from liver and testis of the rat are identical enzymes having extremely similar properties to mice erythrocyte G6PD. The microsomal G6PD of both organs are not homologous enzymes. Testicular microsomal G6PD is likely to be an organ specific G6PD-isoenzyme.

Animals↗
PubMedDate not supplied

Molecular and biochemical data on some glucose-6-phosphate dehydrogenase variants from southern Sardinia.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD; E.C.1.1.1.49) deficiency is the most common human enzymopathy; nearly 400 different biochemical variants of the enzyme have been described. Sardinia is the Italian region with the highest frequency of this defect. METHODS: We examined genomic DNA of 16 subjects with G6PD Mediterranean, 2 with G6PD Athens-like, 1 with G6PD Ferrara 2 (all as biochemically defined). RESULTS: All G6PD Mediterranean subjects had a C-->T mutation at nucleotide 563 and a C-->T transition at nucleotide 1311; G6PD Athens-like and Ferrara 2 subjects had a G-->C mutation at nucleotide 844 (the same mutation has been found in G6PD Seattle-like). CONCLUSIONS: This study suggests that in Southern Sardinia G6PD mutations are relatively homogeneous and that the results of biochemical characterization studies must be carefully evaluated, because the same mutations might be responsible for different biochemical behavior.

Genetic Variation↗
PubMed1994

Expression and biochemical characterization of human glucose-6-phosphate dehydrogenase in Escherichia coli: a system to analyze normal and mutant enzymes.

We have developed a system to characterize normal and mutated glucose-6-phosphate dehydrogenase (G6PD) enzymes in vitro. Normal or mutant G6PD cDNA was subcloned into a pGEX-3X vector, which allowed production of a functional fusion protein in Escherichia coli. When we compared the recombinant normal enzyme with authentic human G6PD, indistinguishable Km values for glucose-6-phosphate (G6P) and NADP were obtained, and the utilization rates for two substrate analogues (2-deoxy G6P and deamino NADP) also showed no difference between the enzymes. This system was used to assay a biochemically uncharacterized variant, G6PD Taipei (493 A-->G; 165 Asn-->Asp), plus two other known mutations (487 G-->A; 163 Gly-->Ser and 592 C-->T; 198 Arg-->Cys) that are located close to or within the putative G6P binding domain. Our results show that the G6PD activities of these three mutants were greatly reduced. No significant alteration in G6PD kinetics was observed for both 487 and 493 mutations. However, a drastic reduction in the Km for G6P (4-fold decrease) and tremendous increases in utilization rates of 2-deoxy G6P (32-fold increase) and deamino NADP (6-fold increase) were associated with the 592 mutation. This results suggests that arginine 198 in human G6PD, possibly located within the putative G6P binding domain, may play an important role in binding the substrate G6P. In addition, we and others have recently identified that at least nine different types of mutations are responsible for G6PD deficiency in Chinese. In this report, we also present the occurrence rate of each mutation present in the population of Taiwan.

Base Sequence↗
PubMed1996

Glucose-6-phosphate dehydrogenase deficiency mutations in Papua New Guinea.

We characterize the molecular basis of two G6PD deficiency variants from Papua New Guinea (PNG) and use the information to examine the extent of molecular heterogeneity underlying G6PD variation in the country. The Wosera G6PD- enzyme was found in a male from the East Sepik Province; it had unique biochemical characteristics compared with other previously described G6PD variants from PNG. The Wosera mutation occurred in exon 12 and led to an Arg463-->His substitution. The Kalo mutation, which led to G6PD deficiency in a male from the Central Province along the south coast of PNG, was found in exon 11 and resulted in an Arg454-->Cys substitution. Although screening for the two molecular mutations using sequence-specific oligonucleotide (SSO) hybridization revealed a wide distribution for the Kalo variant along the coastal belt, no additional copy of the Wosera variant was found in a range of samples. Moreover, 28 G6PD- genes from various parts of PNG failed to hybridize with oligonucleotides encoding either the Kalo or Wosera variants. This suggests that more than the two G6PD mutations exist in PNG, confirming the previously noted biochemical heterogeneity of G6PD deficiency in the Melanesian populations of this region.

Base Sequence↗
PubMed1997

Two novel glucose 6-phosphate dehydrogenase deficiency mutations and association of such mutations with F8C/G6PD haplotype in Chinese.

Glucose 6-phosphate dehydrogenase (G6PD) deficiency is a common genetic disease affecting 3% of the total Chinese population in Taiwan. To investigate the molecular basis of this deficiency, we analyzed blood samples from G6PD-deficient newborns using a nonradioactive polymerase chain reaction coupled with single-stranded conformation polymorphism (PCR-SSCP) analysis. We identified two novel G6PD mutations in Chinese. The first, G6PD Miaoli, involved a C-->G substitution at nucleotide (nt) 519, producing a Phe173 to Leu change in the protein. The second mutation (G6PD Keelung) involved a C-->T change at nt 1387, resulting in an Arg463 to Cys substitution. The F8C/G6PD (coagulation factor VIIIc) haplotype that spans the Xq28 region from the gene for coagulation factor VIIIc to the gene for G6PD was also investigated in Chinese using PCR and restriction enzyme digestion. Of the 16 possible haplotypes, only four were found, which suggests that these four polymorphic sites are in strong linkage disequilibrium. Analysis of the association of G6PD mutations with F8C/G6PD haplotype revealed that nt 517, 592, 835, and 1387 mutations are linked to haplotype VI+VII, whereas the nt 519 mutation is linked to haplotype III. The finding that some G6PD mutations are associated with a particular F8C/G6PD haplotype may be useful for future population studies.

Female↗
PubMed1998

Polyunsaturated fatty acids inhibit the expression of the glucose-6-phosphate dehydrogenase gene in primary rat hepatocytes by a nuclear posttranscriptional mechanism.

Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene is inhibited by the addition of polyunsaturated fatty acids to the medium of primary hepatocytes in culture. To define the regulated step, we measured the abundance of G6PD mRNA both in the nucleus and in total RNA and measured the transcriptional activity of the G6PD gene. Insulin and glucose stimulated a 5- to 7-fold increase in G6PD mRNA in rat hepatocytes. This increase was attenuated by 60% due to the addition of arachidonic acid. These changes in mRNA accumulation occurred in the absence of changes in the rate of transcription. Amounts of precursor mRNA (pre-mRNA) for G6PD in the nucleus changed in parallel with the amount of mature mRNA. The decrease in G6PD pre-mRNA accumulation caused by arachidonic acid was also observed with other long chain polyunsaturated fatty acids but not with monounsaturated fatty acids. In addition, this decrease was not due to a generalized toxicity of the cells due to fatty acid oxidation. These changes in G6PD expression in the primary hepatocytes are qualitatively and quantitatively similar to the changes observed in the intact animal due to dietary carbohydrate and polyunsaturated fat. Regulation of G6PD expression by a nuclear posttranscriptional mechanism represents a novel form of regulation by fatty acids.

Animals↗