Le Phenotype Research Articles

The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses.

BackgroundGlutaric acidemia type I (GA1) is an organic acidemia that is often unrecognized in the newborn period until patients suffer an acute encephalopathic crisis, which can be mistaken for nonaccidental trauma. Presymptomatic identification of GA1 patients is possible by newborn screening (NBS). However, the biochemical “low‐excretor” (LE) phenotype with nearly normal levels of disease metabolites can be overlooked, which may result in untreated disease and irreversible neurological sequelae. The LE phenotype is also a potential source of false negative (FN) NBS results that merits further investigation.MethodsSamples from six LE GA1 patients were analyzed by biochemical and molecular methods and newborn screen outcomes were retrospectively investigated.ResultsFive LE GA1 patients were identified that had normal NBS results and three of these presented clinically with GA1 symptoms. One additional symptomatic patient was identified who did not undergo screening. Semiquantitative urine organic acid analysis was consistent with a GA1 diagnosis in two (33%) of the six patients, while plasma glutarylcarnitine was elevated in four (67%) of the six and urine glutarylcarnitine was elevated in four (80%) of five patients. Five GCDH variants were identified in these patients; three of which have not been previously linked to the biochemical LE phenotype.ConclusionsThe data presented here raise awareness of potential FN NBS results for LE GA1 patients. The LE phenotype is not protective against adverse clinical outcomes, and the possibility of FN NBS results calls for high vigilance amongst clinicians, even in the setting of a normal NBS result.

Prevalence of major blood group antigens in blood donors at a main donation center in United Arab Emirates.

Abstract Blood transfusion is a common practice in hospitals. In many diseases, transfusion of red blood cells can be a life-saving measure. Knowing the blood group phenotypes of the donors in any population is important to improve health care services and to better serve patients. We aimed to determine the blood group phenotypes of the regular donors visiting the main blood donation center in Sharjah, United Arab Emirates (UAE). A total of 500 regular blood donors were included, and blood group antigens were tested using serologic methods. Major blood group systems included in this testing were ABO, Rh, Kell, Kidd, Duffy, Lewis, Lutheran, MNS, and P1PK. The most prevalent ABO/D blood type was group O, D+ (29.6%), with the most prevalent phenotype in the Rh blood group system reported as R1r (34.4%). In the Kell system, the K–k+ phenotype was reported in 92.4 percent of individuals tested. The rare Duffy null phenotype, Fy(a–b–), was reported in 11.0 percent of the cohort. Most donors (99.0%) were Lu(b+). In the Lewis system, the phenotype Le(a–b+) was seen in 61.8 percent of the donors. MNS system phenotypes were comparable to the reports from Saudi Arabia and India, with M+N+S–s+ being the most prevalent (21.2%). The prevalence of many major blood group phenotypes in the UAE blood donor population showed similarities to results from populations in neighboring countries, but other phenotype prevalences were unique to this population. This finding can be used to build a blood group registry for the local population that can better serve hospitals’ transfusion requirements.

Differential expression of genes encoding phenylpropanoid enzymes in an apricot cultivar (Prunus armeniaca L.) with cleavable endocarp

Phenylpropanoid pathway related genes were identified and analyzed by co-expression network and expression pattern. NST1 may regulate the expression of CAD to affect the lignin deposition of ‘Liehe’ apricot endocarp. Apricot (Prunus Armeniaca L.) is a typical Rosaceae stone fruit tree. The extensive lignification of its endocarp is an important metabolic event during fruit ripening. There are abundant apricot germplasm resources in China, including a special apricot cultivar, ‘Liehe’ (LE), which has a thin, soft, cleavable endocarp with a hardness 45.84% that of the ‘Jinxihong’ (JG) apricot (with normal hardened-endocarp). To understand the molecular mechanisms behind the LE phenotype, differentially expressed genes (DEGs) encoding key enzymes involved in phenylpropanoid biosynthesis were mined from transcriptome data by the co-expression network and expression patterns. DEGs encoding key enzymes involved in phenylpropanoid biosynthesis were significantly down-regulated in LE, and the activity of these enzymes exhibited similar results. NST1 (NAC secondary wall thickening promoting factor 1) expression levels in LE were only 13.7%, 2.8%, 9.4%, and 82.5% that in JG at 9, 15, 21, and 30 days after full bloom (DAFB), respectively. CAD (Cinnamyl alcohol dehydrogenase) expression levels in LE were 1.3%, 0.7%, 0.2% and 2.7% that in JG at 15, 21, 30, 49 DAFB, respectively. CAD activity in LE was 46.4% and 63.6% that in JG at 42 and 49 DAFB, respectively. We thus used homologous cloning to determine the sequence differences of CAD and NST1 in LE and JG. Our results will help understand the molecular mechanisms underlying endocarp cleavage in LE apricot and provide a useful reference for further investigation of lignification during endocarp development. NST1 may regulate CAD which involved in the phenylpropanoid pathway and affect lignin deposition in LE endocarp.

Prevalence of Lewis Blood Group among Bangladeshi Population

Background: The Lewis system differs from all other blood group systems. It is primarily a system of soluble antigens originate in the tissue of body secretions, such as saliva (glycoprotein) and in plasma (glycolipid) respectively.The ABH secretor status influences red cells of Lewis phenotype and this phenotype may be modified by the ABO phenotype.Methodology: A cross sectional study was done to determine the presence of Lewis antigens in patients and voluntary donor's blood and observe the agglutination pattern during blood cross matching. In this study 350 blood samples were tested by hemagglutination -monoclonal antibodies.Result: Our study showed, Lewis antibody was detected in 50.8 % cases. The presence of anti-Leb was more frequent (69.7%) than anti-Lea in association with ABO blood group. Lewis anti-Leb was most common in O group (75.0%) followed by group-A (69.0%) where as anti-Lea was predominant in B (37.7%) followed by AB (33.3%).Moreover among Lewis phenotypes, Le (a-b+) was present in 35.4% cases, Le (a+ b-) in 15.1% and Le (a+ b+) was rare (0.3%). Phenotype Le (a-b-) represents all negative cases 172 in number (49.2%).Conclusion: Presence of Lewis antibody cause irregular agglutination interfering with interpretation of compatibility testing. So the patients with multiple transfusions or having atypical or irregular antibodies should routinely test for Lewis blood group antibodies to avoid untoward reactions.Anwer Khan Modern Medical College Journal Vol. 7, No. 2: Jul 2016, P 12-15

The M405V allele of the glutaryl-CoA dehydrogenase gene is an important marker for glutaric aciduria type I (GA-I) low excretors.

Glutaric aciduria type I (GA-I) is an autosomal recessive organic aciduria resulting from a functional deficiency of glutaryl-CoA dehydrogenase, encoded by GCDH. Two clinically indistinguishable diagnostic subgroups of GA-I are known; low and high excretors (LEs and HEs, respectively). Early medical and dietary interventions can result in significantly better outcomes and improved quality of life for patients with GA-I. We report on nine cases of GA-I LE patients all sharing the M405V allele with two cases missed by newborn screening (NBS) using tandem mass spectrometry (MS/MS). We describe a novel case with the known pathogenic M405V variant and a novel V133L variant, and present updated and previously unreported clinical, biochemical, functional and molecular data on eight other patients all sharing the M405V allele. Three of the nine patients are of African American ancestry, with two as siblings. GCDH activity was assayed in six of the nine patients and varied from 4 to 25% of the control mean. We support the use of urine glutarylcarnitine as a biochemical marker of GA-I by demonstrating that glutarylcarnitine is efficiently cleared by the kidney (50-90%) and that plasma and urine glutarylcarnitine follow a linear relationship. We report the allele frequencies for three known GA-I LE GCDH variants (M405V, V400M and R227P) and note that both the M405V and V400M variants are significantly more common in the population of African ancestry compared to the general population. This report highlights the M405V allele as another important molecular marker in patients with the GA-I LE phenotype. Therefore, the incorporation into newborn screening of molecular screening for the M405V and V400M variants in conjunction with MS/MS could help identify asymptomatic at-risk GA-I LE patients that could potentially be missed by current NBS programs.

Evaluation of Lewis blood group antigens and secretor status in pemphigus vulgaris.

There has not been publication of any previous study about the role of secretory status or Lewis phenotypes in the mechanisms of pemphigus vulgaris (PV). To evaluate the frequencies of secretory status and Lewis phenotypes in patients with PV compared with healthy controls (HCs) in order determine their roles in this autoimmune disease. In total, 50 patients and 100 age- and sex-matched HCs were selected to form the study population, and 2mL blood were collected from each subject to identify their Lewis phenotype. In subjects with the Le(a-b-) phenotype, saliva was also collected to determine secretor status. The frequency of the nonsecretor (NS) phenotypes Le(a+b-) and Le(a-b-) together was significantly higher in patients than in HCs: 34/50 (68%)vs. 26/100 (26%), respectively (P<0.001). All the patients and HC subjects with the Le(a-b-) phenotype were found to be NS by haemagglutination inhibition assay of saliva samples. Based on our results, it seems that Le/b-negative NS individuals are more susceptible to PV.

65 Miglustat therapy ameliorates bone mass and bone formation in F508del cystic fibrosis mice

In CF patients with the F508del mutation, vertebral fractures and subsequent dorsal kyphosis decrease pulmonary function, thus accelerating the course of the disease. We discovered a defective CFTR-mediated Cl− channel activity and deficit of osteoprotegerin production by primary osteoblasts (the cells that form bone) of a 25-yr-old CF male (Gimenez A., 2012). Homozygous F508del-CFTR mice exhibit a severe osteopenic phenotype (Le Henaff C., 2012). Miglustat (N butyldeoxynojyrimicin) was reported to normalize CFTR-dependent chloride transport in nasal mucosa in F508del CF mice. We evaluated the efficacy of oral miglustat treatment in restoring bone mass in CF mice. The bone microarchitecture of CF mice, relative to wild type (WT) littermates was evaluated after an administration of 120mg/kg/day miglustat for 28 days using in vivo micro-CT, bone histomorphometry and dynamic parameters of bone formation. Levels of two serum growth factors, insulin-like growth factor 1 (IGF-1) and 17b-estradiol (E2) were determined. A once-a-day oral treatment with miglustat normalized bone volume and improved bone micro-architecture of the lumbar spine in CF mice after 4 weeks. This increase of bone volume was accompanied to both an increased bone formation and serum E2 level with no changes in IGF-1 level in miglustat-treated F508del mice. This study provides first evidence that oral administration of miglustat increases bone mass and formation in CF mice; these findings support the therapeutic potential of miglustat in patients with CF-related bone disease. Supported by Association Vaincre la Mucoviscidose, France; miglustat kindly provided by Actelion Pharmaceuticals, Switzerland.

Genotypic and Phenotypic Variation of Lewis Antigen Expression in Geographically Diverse Helicobacter pylori Isolates

Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and β-(1,3)galT loci in 113 H. pylori strains. Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le(a) and Le(b) ) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression.

Determinants of Obesity Among Men with the Lewis Double-Negative Blood Group: A Genetic Marker of Obesity—The Copenhagen Male Study

Middle-aged and elderly men with the Lewis blood group phenotype Le(a-b-), have a two-fold higher prevalence of obesity than others. We investigated if the association could be ascribed to differences in lifestyle, or if obesity determinants had a different impact in this group. This was a cross-sectional study of 3,290 men aged 53-74 years with a mean of 63 years drawn from the Copenhagen Male Study. The main outcome measure was prevalence of obesity [body mass index (BMI) ≥30 (kg/m(2))]. Among men with the Le(a-b-) phenotype (n = 315), the prevalence of obesity was 15.6%; it was 8.1% among men with other phenotypes (n = 2,975, p < 0.001). Obesity-related life style habits did not differ between Le(a-b-) and other men. In multiple logistic regression analyses, the role of obesity covariates was conspicuously different between men with the Le(a-b-) phenotype and men with other Lewis phenotypes. However, among Le(a-b-) men, a much stronger inverse association was found between high coffee consumption (>7 cups/day vs. less) and obesity, and between lacking fat avoidance and obesity; the odds ratio [95% confidence interval (CI)] for high coffee consumption was 0.2(0.1-0.7) and for avoidance of fatty foods 2.0(1.04-3.7). The association of obesity with leisure time physical activity, smoking, alcohol use, use of sugar in hot beverages, and tea consumption, did not differ between Le(a-b-) men and others. Our findings suggests a gene-environment interaction between lifestyle and obesity. Because some ethnic groups have up to 40% with the Le(a-b-) phenotype, the above observations may be of significant public health interest.

Host-dependent Lewis (Le) antigen expression in Helicobacter pylori cells recovered from Leb-transgenic mice

Variation of surface antigen expression is a mechanism used by microbes to adapt to and persist within their host habitats. Helicobacter pylori, a persistent bacterial colonizer of the human stomach, can alter its surface Lewis (Le) antigen expression. We examined H. pylori colonization in mice to test the hypothesis that host phenotype selects for H. pylori (Le) phenotypes. When wild-type and Leb-expressing transgenic FVB/N mice were challenged with H. pylori strain HP1, expressing Lex and Ley, we found that bacterial populations recovered after 8 mo from Leb-transgenic, but not wild-type, mice expressed Leb. Changes in Le phenotype were linked to variation of a putative galactosyltransferase gene (β-(1,3)galT); mutagenesis and complementation revealed its essential role in type I antigen expression. These studies indicate that H. pylori evolves to resemble the host's gastric Le phenotype, and reveal a bacterial genetic locus that is subject to host-driven selection pressure.

Blood Group Lewis Alloantibodies Cause Antibody-Mediated Rejection in Renal Transplant Recipients

Three patients with negative Lewis phenotypes who displayed anti-Lewis antibodies suffered severe kidney allograft dysfunction. One woman and two men (22–44 years) received ABO compatible kidney transplants with negative donor-recipient cross-match tests. Two patients had the phenotype Le(a−b−) with anti-Le(a) and anti-Le(b) complement binding antibodies. The third patient of phenotype Le(a+b−) developed anti-Lewis(b) antibody a few months after transplantation. One patient presented recurrence of worsened graft function from the day 6 to 4 months after transplantation; despite treatment there was not full recovery. The second patient had recurrences of acute graft dysfunction at 4 and 6 months after transplantation with nephrotic range proteinuria. The third patient showed progressive graft dysfunction at 7 months after transplantation. Biopsy specimens showed histological changes of antibody-mediated rejection. In the third patient, we observed fibrinoid necrosis and thrombosis of arterioles and glomerular capillaries. Immunofluorescence studies showed immunoglobulin IgG and IgM in glomerular capillaries and C4d and C3 on endothelial cells of peritubular capillaries. Posttransplantation cross-match tests with donor lymphocytes were negative. Anti-Lewis antibodies were observed during follow-up. All patients were treated with methylprednisolone boluses. In addition, one subject received antithymocyte globulin (ATG) and 1 received plasmapheresis. Two patients had moderate renal dysfunction (creatinine levels 1.8 and 1.9 mg/dL) after 8–17 months follow-up. The third patient lost her graft at 11 months after transplantation. Lewis antibodies may injure a renal allograft. C4d deposition and failure to show donor-specific anti-HLA antibodies suggested the participation of other antibodies.

Role of futC slipped strand mispairing in Helicobacter pylori Lewis y phase variation

The O antigen of the Helicobacter pylori lipopolysaccharide is composed of repeating units of fucosylated Lewis (Le) antigens. The α(1,2)-fucosyltransferase ( futC) of H. pylori, which catalyzes the conversion of Le x to Le y by addition of fucose, is subject to slipped-strand mispairing involving a homonucleotide (poly-C) tract. To explore the distribution of Le phenotypes within H. pylori cells grown in vitro, 379 single colonies of strain J166 were examined for Le expression. Two major populations with reciprocal Le x/Le y phenotypes were identified. Phenotypes correlated with futC frame status, suggesting that strain J166 represents a mixed population with respect to futC poly-C tract length, which was confirmed by a translational reporter. After hundreds of generations in vitro, phenotypes did not change significantly, indicating that the observed J166 Le diversity reflects the founding population. Since slipped-strand mispairing in the futC poly-C tract was postulated to explain the Le y phenotypic change observed in J166 derivative strain 98–169 isolated 10 months after rhesus monkey challenge, in trans complementation with in-frame futC was performed. Le y synthesis was restored and Le x expression was reciprocally lowered. From these studies, we confirmed the principal role of futC slipped-strand mispairing in Le antigenic variation in vitro and in vivo.

Genetic Markers and Psoriasis in Three Ethnic Populations of Dagestan

Analysis of clinical material obtained from the individuals (49 psoriasis patients and 357 individuals without this disease) representing three ethnic populations of Dagestan (Avars, Dargins, and Kumyks) was performed. Polymorphism of the blood group loci AB0, Rhesus (RH), Kell, P, and Lewis, as well as of the protein-encoding loci for haptoglobin (HP), group-specific component (GC), and the enzymes, including glycosylase (GL01), esterase D (ESD), 6-phosphate dehydrogenase (6PDG), and acid phosphatase (ACP), was studied. It was demonstrated that in the pooled sample of Avars and Kumyks the Lewis system phenotype Le(a-b-) and the RH homozygotes (ee/ee) were statistically significantly more frequent among the psoriasis patients (P = 0.0488 and P = 0.0166, respectively), than among healthy controls of the same ethnic groups. It was suggested that for the pooled sample of Avars and Kumyks, homozygosity for the recessive RH allele (ee/ee) in combination with the Le(a-b-) phenotype, representing homozygosity for recessive allele le, was the risk factor for the development of psoriasis.

The Lewis blood group—a new genetic marker of obesity

In a cross-sectional epidemiological study including 3290 men aged 53-75 y, mean=63, we tested the hypothesis that the Lewis phenotype Le(a-b-) is a genetic marker of obesity. All men were Lewis typed and measurements were made of height, weight, neck circumference, and hip fat fold. Obesity was defined as a body mass index >/=30 kg/m(2). Totally 291 men (8.8%) were obese; 9.6% of the men had the Le(a-b-) phenotype. Le(a-b-) men had a higher prevalence of obesity than others, 15.6 vs 8.1%, odds ratio (95% confidence interval): 2.1(1.5-2.9), P<0.001. The etiological fraction, that is, the excess prevalence of obesity in the study population due to the Le(a-b-) phenotype, was approximately 10%. The frequency of the Le(a-b-) phenotype may vary substantially in different populations. Identification of this new genetic marker of obesity may, for example, contribute to the explanation of individual and ethnic differences in the prevalence of obesity.

Association of Lewis blood group phenotype with preterm premature rupture of membranes.

To evaluate the distribution of Lewis blood group phenotype and secretor status among women with preterm premature rupture of membranes. ABO and Lewis blood group phenotypes were determined in 20 consecutive women with preterm premature rupture of membranes. The control group was composed of 48 women from our database without known history of preterm delivery. Of the 20 patients with preterm premature rupture of membranes six had blood type A (30%), nine type B (45%), two type AB (10%), three type O (15%), three Le(a(-)b(+)) (15%), one Le(a(+)b(-)) (5%), and 17 had Le(a(-)b(-)) (80%). Of the 48 controls, 18 had blood type A (37.5%), 10 type B (20.9%), two type AB (4.1%), 18 type O (37.5%), 37 Le(a(-)b(+)) (77.1%), six Le(a(+)b(-)) (12.5%), and five had Le(a(-)b(-)) (10.4%). The difference in the proportions of the A, B, AB, and O phenotypes between the groups was not statistically significant. The distribution of ABO and Lewis phenotype in the control group was similar to that in the general population. The proportion of combined recessive and nonsecretor phenotypes Le(a(+/-)b(-)) between patients with preterm premature rupture of membranes (17 of 20, 85%) and controls (11 of 48, 22.9%) was statistically significant (P <.001). Women with the Le(a(-)b(+)) phenotype who do secrete Le(b) antigen may have a protective effect against preterm premature rupture of membranes.

Prevalence of lewis phenotype (le) in patients suffering from pancreatic diseases

Prevalence of lewis phenotype (le) in patients suffering from pancreatic diseases

Relationship of anti-Lewis x and anti-Lewis y antibodies in serum samples from gastric cancer and chronic gastritis patients to Helicobacter pylori-mediated autoimmunity.

Lewis (Le) antigens have been implicated in the pathogenesis of atrophic gastritis and gastric cancer in the setting of Helicobacter pylori infection, and H. pylori-induced anti-Le antibodies have been described that cross-react with the gastric mucosa of both mice and humans. The aim of this study was to examine the presence of anti-Le antibodies in patients with H. pylori infection and gastric cancer and to examine the relationships between anti-Le antibody production, bacterial Le expression, gastric histopathology, and host Le erythrocyte phenotype. Anti-Le antibody production and H. pylori Le expression were determined by enzyme-linked immunosorbent assay, erythrocyte Le phenotype was examined by agglutination assays, and histology was scored blindly. Significant levels of anti-Le(x) antibody (P < 0.0001, T = 76.4, DF = 5) and anti-Le(y) antibody (P < 0.0001, T = 73.05, DF = 5) were found in the sera of patients with gastric cancer and other H. pylori-associated pathology compared with H. pylori-negative controls. Following incubation of patient sera with synthetic Le glycoconjugates, anti-Le(x) and -Le(y) autoantibody binding was abolished. The degree of the anti-Le(x) and -Le(y) antibody response was unrelated to the host Le phenotype but was significantly associated with the bacterial expression of Le(x) (r = 0.863, r(2) = 0.745, P < 0.0001) and Le(y) (r = 0.796, r(2) = 0.634, P < 0.0001), respectively. Collectively, these data suggest that anti-Le antibodies are present in most patients with H. pylori infection, including those with gastric cancer, that variability exists in the strength of the anti-Le response, and that this response is independent of the host Le phenotype but related to the bacterial Le phenotype.

A Comparison of Lewis X and Lewis Y Expression inHelicobacter pyloriObtained from Children and Adults

There are no reports, to our knowledge, on the expression of Lewis (Le) antigens in Helicobacter pylori isolates from children. The aim of this study was to compare the expression of Le antigens by H. pylori isolates from children and from adults. Totals of 278 clones from 22 children with recurrent abdominal pain and 293 clones from 22 adults with (n=10) or without (n=12) duodenal ulcer were studied. Expression of Le(x) and Le(y) antigens was determined by ELISA, using monoclonal anti-Le antibodies. The Le phenotype of the patients was determined in gastric juice with a hemagglutination assay. Clones expressing Le(x) were more common in children than in adults (55.4% vs. 33.4%, respectively; P<.001), and Le(y) was more common in adults than in children (81.6% vs. 66%, respectively; P<.01). A trend analysis showed a significant decline in frequency of clones expressing Le(x) with age (P=.021). In this community, expression of Le antigens differs in H. pylori isolates obtained from children versus adults.

Molecular characterization of secretor type alpha(1, 2)-fucosyltransferase gene deficiency in the Philippine population.

We analyzed the seven mutations which are responsible for the deficiency of the secretor type alpha(1,2)-fucosyltransferase gene product, Se enzyme, in the Philippine population. One hundred and one unrelated Filipinos in Taiwan were studied. A new mutation, a 3-base pair deletion from nt 688 through 690, was found in two (0. 1%) of 202 chromosomes. The frequencies of six other mutated alleles were as follows: 71/202 (35.2%) were cDNA 385 A-->T missensed mutation (se2), 28/202 (13.9%) were C571T nonsense mutation (se3), 16/202 (7.9%) were G849A nonsense mutation (se4), 4/202 (1.9%) were G428A nonsense mutation (se1), and 81/202 (40.1%) were wild-type allele (Se). No C628T nonsense mutations (se5) or fusion genes of pseudogene and FUT2 gene (se 6) were found in this population. For the molecular basis of phenotype Le(a+ b-): eight cases had se2/se2, six cases had se2/se3, two cases had se3/se4, one case was homozygous of se4, one case was se3/se1, and two cases were se2/se7. For the Le(a+ b+) phenotype: four cases had se2/se2, two cases had se2/se3, one case was se3/se3, and one case was se2/se4. For the Le(a- b+) phenotype: 16 cases were Se/Se, 21 cases were Se/se2, six cases were Se/se3, five cases were Se/se4, and two cases had Se/se1. Our results suggest that the genotypes of the alpha(1, 2)-fucosyltransferase gene in phenotypes Le(a+ b+) and Le(a+ b-) are the same. Other factors that play important roles may cause the differences between these two phenotypes. Several hotspot mutations in the alpha(1,2)-fucosyltransferase gene are responsible for the nonsecretor phenotype.

Molecular analysis of secretor type alpha(1,2)-fucosyltransferase gene mutations in the Chinese and Thai populations.

The human Lewis histo-blood group system belongs to a family of structurally related oligosaccharides. The mutations of fucosyltransferase genes alpha(1,2)-fucosyltransferase (FUT2 or Se) and alpha(1,3/1,4)-fucosyltransferase (FUT3 or Le), are responsible for the polymorphism of Lewis blood group phenotypes. However, a population study of the FUT2 mutation in Chinese and Thais has not yet been done, and there is some controversy about the phenotypes of Le(a+b+) and Le(a+b-). One hundred twentyfour Chinese and 70 Thais were phenotyped for Lea and Le(b). DNA samples were studied by polymerase chain reaction and then by a restriction enzyme digestion method to distinguish wild-type and six known mutations. Direct sequencing was done for controls and some uncertain cases. A new mutation, C302T mutation, was found in 2 of 136 chromosomes in the Thai population; none were discovered in Chinese. The frequencies of the normal and six mutant alleles among Chinese and Thais, respectively, were as follows: 134 (54.0%) of 248 and 58 (41.4%) of 140 were wild-type (Se); 0 of 248 and 2 of 140 (both 1.4%) had the G428A mutation; 120 (48.4%) of 248 and 75 (53.6%) of 140 had the A385T mutation; 2 (0.81%) of 248 and 0 of 140 had the C571T mutation; and 1 (0.4%) of 248 and 3 (2.2%) of 140 had the G849A mutation. Only 1 Chinese (0.4%) of 248 had the C628T mutation, and none had fusion gene mutation. The FUT2 genes encoding for the phenotypes Le(a+b+) and Le(a+b-) are the same. The function and character of the mutant enzyme may play an important role in the phenotype. The methods used in this study are clinically applicable in population studies of the FUT2 gene polymorphism to explore relationships among different ethnic groups and correlations between phenotype and genotype.