广州地区汉族人群HNA-1基因频率分布的研究

目的了解广州地区汉族人群HNA-1基因的多态性及频率分布情况。方法采用序列特异性引物-聚合酶链反应(PCR-SSP)对150名广州地区汉族健康献血者作HNA-1基因分型,计算HNA-1等位基因频率并进行Hardy-Weinberg平衡检验;将结果与国内外部分数据比较。结果广州地区汉族人群HNA-1a、1b等位基因频率分别为0.713、0.287,未发现HNA-1c等位基因;人群基因型以HNA-1aa(50%)纯合子和HNA-1ab(43%)杂合子为主要表达形式;广州地区汉族人群HNA-1基因频率与浙江汉族、西藏藏族、大连汉族、西北回族、日本、韩国、德国、西班牙人群比较差异具有统计学意义(P<0.05)。结论得出了广州地区汉族人群HNA-1的基因频率的分布情况,为临床上相关疾病的诊治和预测提供一定的实验数据基础。     

A novel enzyme-linked immunosorbent assay method for the detection of human neutrophil antigen-2a antibodies

BACKGROUND: Antibodies to human neutrophil antigen (HNA)-2a are responsible for a number of immune-mediated neutropenia disorders. Although several methods exist for the identification of anti-HNA-2a, all these methods have several limitations. In this study, a solid-phase enzyme-linked immunosorbent assay (ELISA) using recombinant HNA-2a antigen (rHNA-2a) allowing rapid detection of HNA-2a antibodies was developed.
STUDY DESIGN AND METHODS: Soluble rHNA-2 was generated by transfection of insect cells with CD177 vector. Purified rHNA-2a was immobilized on microtiter wells coated with anti-CD177 and was applied to analyze 10 sera containing HNA-2a antibodies. For the evaluation of the ELISA method, results were compared with the standard assay, MAIGA (monoclonal antibody antigen capture assay) for detection of neutrophil antibodies.
RESULTS: The specificity of HNA-2a antibodies in all sera was confirmed by immunoblotting. Sera were then tested simultaneously in ELISA and MAIGA assays. Nine of 10 sera showed positive reactions in ELISA, whereas only 9 of 10 sera reacted in the standard MAIGA assay. All HNA-2a antibodies were detectable in MAIGA when diluted sera were applied. No reaction was observed with different sera containing neutrophil-reactive antibodies (6 anti-HNA-1a, 4 anti-HNA-1b, and 20 anti-HLA Class I and II) in ELISA. All HNA-2a antibodies were detectable in MAIGA when diluted sera were applied. Notably, sera containing anti-proteinase 3 (PR3) from patients with Wegener's granulomatosis reacted in MAIGA. In contrast, this antibody showed no reaction in ELISA with purified rHNA-2a.
CONCLUSIONS: These results demonstrated that ELISA with rHNA-2a provides a good method for detecting HNA-2a antibodies in human serum. This assay enables to exclude the presence of autoantibody against PR3 in patient's sera, which cannot be differentiated from anti HNA-2a with current serologic methods.     

SLC2A3 variants in familial and sporadic congenital heart diseases in a Chinese Yunnan population

BackgroundSolute carrier family 2 member 3 (SLC2A3), is a member of a superfamily of transport protein genes. SLC2A3 played an important role in embryonic development. Previous research reported SLC2A3 duplication was reportedly associated with congenital syndromic heart defects. However, it is not clear whether the gene is associated with non‐syndromic congenital heart disease. Our study aimed to elucidate the relationship between its variation and congenital heart disease.MethodsGenomic DNA extracted from the peripheral blood leukocytes of two families with CHD were sequenced with whole‐exome sequencing to identify variations, used Sanger sequencing to investigate SLC2A3 variants in 494 Chinese patients with CHD and 576 healthy unrelated individuals.ResultsIn members from the two families, three with CHD had the SLC2A3 (rs3931701) C > T variant. Of the 494 patients with CHD, 394 had gene variants (86 had the TT type and 308 had the CT type). Of the 576 healthy controls, 272 participants had gene variants (36 had the TT type and 236 had the CT type). The TT type [p < 0.0001, odds ratio (OR) =7.262, 95% confidence interval (CI) =4.631–11.388] and CT type (p < 0.0001, OR =3.967, 95% CI =2.991–5.263) of SLC2A3 (rs3931701) significantly increased the risk of sporadic ASD in a Chinese Yunnan population.ConclusionsSingle nucleotide variations of SLC2A3, particularly, the SLC2A3 (rs3931701) C > T variant increased the risk of CHD among the studied population.     

Significance of human neutrophil antigen-2a (NB1) expression and neutrophil number in pregnancy

BACKGROUND: Expression of human neutrophil antigen-2a (HNA-2a) is greater in women than in men. The size of the HNA-2a-positive neutrophil population increases with pregnancy. STUDY DESIGN AND METHODS: T he relationship between HNA-2a expression on neutrophils and monocytes, and their relative numbers, was investigated. HNA-2a expression shown as the size of the HNA-2a-positive cell population and the fluorescence intensity on the cells was analyzed using flow cytometry. This investigation was done among 165 pregnant women during pregnancy and postpartum. RESULTS: In normal pregnancy, numbers of neutrophils and monocytes changed in relation to HNA-2a expression. HNA-2a was also expressed intensively on monocytes from some pregnant women in the first and second trimesters. HNA-2a expression and the number of cells markedly decreased postpartum. In threatened premature labor, the number of neutrophils decreased earlier than in normal pregnancy. CONCLUSION: HNA-2a expression may increase soon after fertilization. In this study, the results indicate that the change in the number of neutrophils and monocytes is related to HNA-2a expression.     

CYP3A4*1B and NAT2*14 alleles in a native African population.

Single nucleotide polymorphisms were examined in the cytochrome 450 3A4 (CYP3A4) and N-acetyltransferase 2 (NAT2) genes, which code for major mediators of the metabolism of a wide variety of therapeutic drugs, as well as xenobiotics. We determined, in a population from Guinea-Bissau, the frequencies of CYP3A4 and NAT2 variants expected to be prevalent among Africans, due to the high frequency previously observed in African Americans. The observed frequencies were 72% for CYP3A4*1B and 19.2% for the NAT2 191 G>A variant. The high frequency found for these potentially function-altering polymorphisms suggests the possibility of impaired metabolism through CYP3A4 and NAT2 in this population. Strikingly, the frequency observed for the NAT2 191 G>A single nucleotide polymorphism (SNP), associated with the slow acetylator phenotype, was significantly higher than found in other African populations, suggesting the existence of a west to east gradient across Sub-Saharan Africa. The prevalence of these variants may be relevant with regard to therapeutic efficacy in African populations for it may potentially affect drug clearance and consequently, increase the incidence of side effects and drug-drug interactions.     

Implication of transfected cell lines for the detection of alloantibodies against human neutrophil antigen-3

BACKGROUND: Alloantibodies against human neutrophil antigen‐3 (HNA‐3) are responsible for the fatalities reported in transfusion‐related acute lung injury. Consequently, reliable detection of these alloantibodies is mandatory to improve blood transfusion safety. In this study, we developed stable cell lines for the detection of HNA‐3 antibodies. STUDY DESIGN AND METHODS: HEK293T were transfected with HNA‐3a or HNA‐3b constructs and sorted by flow cytometry according to high surface expression. Transfected cells were tested with sera containing HNA‐3 antibodies in flow cytometry and antibody capture assay (ACA). The results were compared with granulocyte agglutination test and granulocyte immunofluorescence test. RESULTS: In flow cytometry, 12 of 14 HNA‐3a sera reacted specifically with HNA‐3aa cells. One serum sample showed positive reaction with HNA‐3bb cells. All HNA‐3b sera recognized HNA‐3bb cells. No reaction was observed with broad reactive antibodies against HLA Class I. In ACA, all HNA‐3a sera (12/12) showed positive reactivity with HNA‐3aa cells with no cross‐reactivity with HNA‐3bb cells. Again, all HNA‐3b sera reacted with HNA‐3bb cells only. Furthermore, genotyping of 249 individuals detected a new HNA‐3 allele caused by a nucleotide substitution C>T at Position 457 leading to L₁₅₃F mutation in choline transporter‐like protein‐2. This mutation impairs polymerase chain reaction with sequence‐specific primers based HNA‐3a typing. However, analysis with cells expressing F₁₅₃ isoform showed that this mutation did not alter the binding of HNA‐3 antibodies. CONCLUSIONS: This study demonstrated that HEK293T cells expressing stable recombinant HNA‐3 are suitable for the detection of HNA‐3 alloantibodies allowing reliable screening of blood products.     

Expression of human neutrophil antigen-2a (NB1) is increased in pregnancy

BACKGROUND: The expression of human neutrophil antigen-2a (HNA-2a) or NB1 is highly variable. This study investigated variations in neutrophil expression of HNA-2a by comparing the expression of epitopes recognized by three HNA-2a-specific CD177 antibodies among healthy adults and pregnant women. STUDY DESIGN AND METHODS: Flow cytometry was used to compare the neutrophil reactions of three CD177 antibodies (MEM-166, TAG4, and 7D8) among 52 healthy adults. Because HNA-2a expression is greater in women than men, neutrophils were studied from 21 women early in pregnancy and 23 women late in pregnancy. RESULTS: All three CD177 antibodies reacted with two populations of neutrophils: a brightly staining population and a dimly staining population. Among the 52 healthy adults, there was no difference in the mean size of the brightly reactive population of neutrophils recognized by each antibody (46 +/- 23% for MEM-166, 49 +/- 23% for TAG4, and 49 +/- 23% for 7D8), and all three antibodies were specific for HNA-2a. For all three antibodies the size of the antigen bright neutrophil population was greater on neutrophils collected both early and late in pregnancy than in healthy adults. There was no difference in the size of the antigen bright population among neutrophils tested early and late in pregnancy. CONCLUSION: HNA-2a antigen expression increases in pregnancy. Some of the variations in neutrophil expression of HNA-2a among individuals is likely due to differences in gene regulation or differences in post-translational protein modifications rather than gene polymorphisms.     

FCGR3 variants and expression of human neutrophil antigen-1a, -1b,and -1c in the populations of northern Germany and Uganda

BACKGROUND: Human neutrophil antigen-1c (HNA-1c) (SH) has been described as the third alloantigen of the Fc receptor type IIIb (FcgammaRIIIb) for IgG beside the known alloantigens HNA-1a (NA1) and HNA-1b (NA2). Controversy exists on the assignment of the HNA-1c coding gene to the FCGR3B locus and on a possible linkage between the HNA-1c and HNA-1a coding genes. STUDY DESIGN AND METHODS: Two hundred sixty northern German blood donors and 43 individuals from Uganda were typed for FCGR3B*1 (NA1), FCGR3B*2 (NA2), and FCGR3B*3 (SH) by allele-specific PCR. In a subset of FCGR3B*3-positive probands, PCR-amplified FCGR3 fragments were subcloned and sequenced. Transmission of FCGR3B*3 was analyzed in family studies. A possible correlation with the FcgammaRIIIb alloantigen expression was investigated by flow cytometry. RESULTS: In the northern German population, FCGR3B*3 was found exclusively in individuals carrying FCGR3B*1 independent of the existence of FCGR3B*2 at a frequency of 5 percent. In the individuals from Uganda, each possible combination of FCGR3B*1, FCGR3B*2, and FCGR3B*3 was detected. FCGR3B*3 frequency was 34.9 percent. Within both populations, some individuals carried each of the three genotypes. DNA sequencing revealed new FCGR3 variants caused by single nucleotide exchanges at the typical polymorphic positions. In one individual, six different FCGR3 variants were detected. CONCLUSION: The coincidence of the three known FCGR3B alleles varies within the population of Germany and Uganda. Three simultaneous FCGR3B forms may be explained by two gene loci, but the basis of the high number of different variants in some individuals still remains unclear. Possible explanations may be a hypermutation mechanism or a number of FCGR3 higher than expected hitherto.     

TRALI due to granulocyte-agglutinating human neutrophil antigen-3a (5b) alloantibodies in donor plasma: a report of 2 fatalities

BACKGROUND: TRALI is usually an immunologic reaction to WBC antibodies in infused plasma and ranks second only to ABO mismatch as a cause of transfusion-associated death. Implicated donors are usually multiparous women (>/=3 pregnancies). STUDY DESIGN AND METHODS: Two fatal cases of TRALI were evaluated by reviewing clinical and laboratory findings and characterizing alloantibodies present in donor plasma. Investigation for WBC antibodies was by lymphocytotoxicity (LCT), FlowPRA (FlowPRA, One Lambda, Inc.) and granulocyte immunofluorescence and agglutination assays. Patient 1 was a 62-year-old man with chronic T-cell lymphocytic leukemia, and Patient 2 was a 54-year-old woman undergoing a cadaveric kidney transplant. Both patients developed acute respiratory distress and hypotension during (Patient 1) and approximately 30 minutes after (Patient 2) transfusion. Fulminant pulmonary edema ensued in both cases necessitating mechanical ventilation and both patients died within 24 hours of the onset of respiratory complications. RESULTS: The donors of the implicated blood components were women with a history of two pregnancies but no blood transfusions. Weak apparently panreactive granulocyte antibodies were detected with flow cytometry. However, in the granulocyte agglutination test, strong antibodies specific for human neutrophil antigen (HNA)-3a (5b) were identified in both donors. CONCLUSION: It is concluded that female blood donors with only two previous pregnancies can form clinically important granulocyte-reactive alloantibodies leading to fatal TRALI reactions in recipients. The sometimes devastating consequences of TRALI should prompt the development of strategies to prevent or reduce its incidence. Further research is warranted to investigate recipient and donor factors responsible for TRALI, including whether 5b (HNA-3a) alloantibodies are especially prone to cause severe reactions, and to better characterize the HNA-3a (5b) antigen, particularly at the molecular level.     

Frequencies of CYP3A5 genotypes and haplotypes in a Korean population

Background and objective: CYP3A, the drug‐metabolizing enzyme is an important factor in the pharmacokinetics of many drugs. Polymorphism of the CYP3A5 gene is known to influence the functionality of the CYP3A5 enzymes. The full extent of CYP3A5 genetic polymorphism was analysed in a Korean population. Methods: Specific polymerase chain reaction‐restriction fragment length polymorphism tests for CYP 3AP1 through CYP3A5*7 or direct sequencing were used to identify reported CYP3A5 variant alleles, using 194 unrelated samples. Results and discussion: The most frequent single nucleotide polymorphism (SNP) was 6986A>G (CYP3A5*3). The next most frequent SNP was 31611C>T. Haplotype analysis using detected SNPs revealed that the most frequent haplotype was *3A (frequency: 0·724), followed by *1E (frequency: 0·211), *3C (frequency: 0·034) and *1A (frequency: 0·023). We did not find CYP3AP1*3, CYP3A5*6, or *7 in this Korean sample. Conclusion: A large proportion of Koreans may have relatively low levels of metabolically active CYP3A5 protein and therefore may be at risk of high levels of drugs metabolized by this enzyme, after administration of conventional doses.     

CYP3A activity in African American and European American men: population differences and functional effect of the CYP3A4*1B5'-promoter region polymorphism

OBJECTIVE: Cytochrome P4503A (CYP3A) activity exhibits considerable interindividual variability. Possible differences in CYP3A activity were investigated in European American and African American men with the use of midazolam as an in vivo probe. METHODS: Midazolam was simultaneously administered intravenously (1 mg, [15N3]-labeled) and orally (2 mg, unlabeled in capsule form) to 15 young healthy European American men and a similar group of men of African American descent. Plasma concentration-time curves were measured. The subjects were subsequently genotyped with respect to the CYP3A4*B1 polymorphism (A-290G) in the 5'-promoter (nifedipine-specific element) region. RESULTS: The oral bioavailability of midazolam was about equally determined by intestinal and hepatic extraction with CYP3A activity at the former site exhibiting greater variability. Oral bioavailability was related to intestinal metabolism (r = 0.98), whereas hepatic CYP3A activity contributed little to the interindividual variability (r = 0.03). A lower systemic clearance (265+/-54 versus 310+/-56 mL/min; P = .04), but not oral clearance, was observed in African Americans. With one exception, the African Americans possessed a variant CYP3A4*1B allele (4 heterozygotes A/G and 10 homozygote G/G), whereas all of the European Americans were wild-type homozygotes (A/A). Hepatic CYP3A activity and the systemic clearance of midazolam were about 30% lower in G/G homozygotes than in A/A homozygotes (252+/-53 versus 310+/-54 mL/min; P = .02), and a gene-dose effect was present (P = .01). There was no genotype/phenotype relationship with respect to the oral clearance of midazolam. CONCLUSION: Comparison of CYP3A activity between populations is complicated by frequency distribution differences in the regulatory CYP3A4*1B polymorphism and lower hepatic CYP3A activity associated with the variant allele. However, this reduction is modest; therefore no major and clinically important difference in CYP3A activity is present between Americans of African or European descent.     

Frequency distribution of antigens in the human platelet antigen-1 system in the western Indian population

BACKGROUND: Neonatal alloimmune thrombocytopenic purpura (NAITP) occurring because of fetomaternal incompatibility in the human platelet antigen-1 (HPA-1) system is increasingly being detected worldwide. Several studies have reported the frequency and distribution of HPA-1 alleles in different countries and ethnic populations. A paucity of data regarding the frequency of the antigens in the HPA-1 system in the Indian population prompted an undertaking of this study. The molecular method of genotyping the platelet antigens is preferred to serology. It will enable future prenatal diagnosis in mothers suspected to have NAITP so that they can be managed better. STUDY DESIGN AND METHODS: Five hundred six unrelated subjects were screened for the alleles in the HPA-1 system, of which 185 were healthy males and 321 were females. DNA was extracted from the peripheral blood WBCs of these subjects, followed by PCR amplification and agarose gel electrophoresis of the PCR-amplified products. RESULTS: Four hundred two out of 506 subjects (79.44%) were found to be homozygous for HPA-1a. Ninety-nine subjects (19.57%) were heterozygous HPA-1a/HPA-1b, and five subjects out of 506 (0.99%) were homozygous for HPA-1b. CONCLUSION: Homozygosity for HPA-1b exists in the Indian population at a frequency of 0.99 percent, whereas homozygosity for HPA-1a is present in approximately 79 percent of the population. Hence, 0.98 x 0.79 of the females (0.77%) in the reproductive age group are likely to be pregnant with an HPA-1a-positive fetus, leading to a setting in which NAITP might develop. The development of NAITP also depends on the HLA type of the mother; nevertheless, the number of pregnancies in which the fetus is at risk for NAITP in India is quite significant.     

CYP3A4 and MDR1 alleles in a Portuguese population.

Polymorphisms in cytochrome P450 CYP3A4 and multidrug resistance (MDR) 1 genes coding for the important drug-metabolising CYP3A4 and the ATP-binding cassette (ABC) transporter P-glycoprotein (Pgp) are poorly documented in the Portuguese population. In this study we have determined the frequencies of CYP3A4 and MDR1 alleles in Portuguese Caucasians. Both genes were simultaneously analysed as these genes are known to be frequently co-induced and their products to show a pronounced overlap of substrates. CYP3A4 A-392G (CYP3A4*1B), T673C (CYP3A4*2) and MDR1 T-129C, G2677T and C3435T single nucleotide polymorphisms (SNPs) were analysed in 100 individuals from the southern region of the country. We observed a frequency of 4.0% for CYP3A4*1B, not significantly different from that reported on other Caucasian European populations. CYP3A4*2 was found at an allele frequency of 4.5%, constituting the first report of the presence of this allele outside the Finnish population. Significant differences were found concerning the MDR1 C3435T SNP frequency (64.5%) compared with other European populations, while no differences were found concerning G2677T (47.5%) or T-129C (5%) SNPs. Linkage between the C3435T and G2677T SNPs was observed, although not as evidently as documented in other Caucasian populations. No preferential associations were detected between CYP3A4 and MDR1 alleles.     

Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3)

Human organic cation transporters (hOCTs) are expressed in organs of drug absorption and elimination and play an important role in the uptake and elimination of xenobiotics. The purpose of this study was to evaluate the substrate and inhibitory activity of the H2-receptor antagonists ranitidine and famotidine toward hOCTs and to determine the hOCT isoforms involved in the absorption and elimination of these compounds in humans. Inhibition and substrate specificity of hOCT1, hOCT2, and hOCT3 for ranitidine and famotidine were elucidated in cRNA-injected Xenopus laevis oocytes. Ranitidine and famotidine exhibited similarly potent inhibition of [3H]1-methyl-4-phenyl pyridinium uptake into hOCT1-expressing (IC50= 33 and 28 microM, respectively) and hOCT2-expressing oocytes (IC50= 76 and 114 microM, respectively). Famotidine exhibited potent inhibition of hOCT3; in contrast, ranitidine was a moderately weak inhibitor (IC50= 6.7 and 290 microM, respectively). [3H]Ranitidine uptake was stimulated by hOCT1 (Km= 70 +/- 9 microM) and to a much smaller extent by hOCT2. No stimulation of [3H]ranitidine uptake was observed in hOCT3-expressing oocytes. trans-Stimulation and electrophysiology studies suggested that famotidine also is an hOCT1 substrate and exhibits poor or no substrate activity toward hOCT2 and hOCT3. Thus, hOCT1, which is expressed in the intestine and liver, is likely to play a major role in the intestinal absorption and hepatic disposition of ranitidine and famotidine in humans, whereas hOCT2, the major isoform present in the kidney, may play only a minor role in their renal elimination. Famotidine seems to be one of the most potent inhibitors of hOCT3 yet identified.     

Equity of African American Men in Headache in the United States: A Perspective From African American Headache Medicine Specialists (Part 2)

In part 1 of this opinion piece, we described inherent and potential challenges of the equity of African American (AA) men in headache medicine including headache disparities, mistrust, understudied/lack of representation in research, cultural differences, implicit/explicit bias, and the diversity tax. We shared personal experiences related to headache medicine likely faced due to the color of our skin. In part 2, we offer possible solutions to achieve equity for AA men in headache including: (1) addressing head and facial pain disparities and mistrust in AA men; (2) professionalism and inclusion; (3) organizational/departmental leadership buy-in for racial diversity; (4) implicit/explicit and other bias training; (5) diversity panels with open discussion; (6) addressing diversity tax; (7) senior mentorship; (8) increased opportunities for noteworthy and important roles; (9) forming and building alliances and partnerships; (10) diversity leadership training programs; (11) headache awareness, education, and literacy with a focus to underrepresented in medicine trainees and institutions; and (12) focused and supported the recruitment of AA men into headache medicine.     

The frequencies of human neutrophil alloantigens in the Chinese Han population of Guangzhou

BACKGROUND: Antibodies against polymorphic structures on human neutrophil antigens (HNAs) play a role in alloimmune‐mediated neutropenia and are the leading cause of antibody‐mediated transfusion‐related acute lung injury (TRALI). This study aimed to determine the frequencies of HNAs in the major Han ethnic group living in Guangdong Province, Southern China. STUDY DESIGN AND METHODS: A total of 493 healthy Chinese Han blood donors from Guangzhou were recruited. DNA samples were isolated and typed for all five HNA‐1, ‐2, ‐3, ‐4, and ‐5 systems using allele‐specific polymerase chain reaction approaches. Results were compared with available data from other Chinese cohorts and other Asian and Caucasian populations. RESULTS: In this cohort, the gene frequency for HNA‐1a (0.667) was approximately twice that of HNA‐1b (0.333). In contrast to Caucasian populations, HNA‐1a represents the most frequent allele in the Chinese population. HNA‐3 system genotyping revealed comparable frequencies for HNA‐3a (0.738) and ‐3b (0.262) in Chinese and Caucasian populations. Homozygous HNA‐3bb individuals were found in 5.64% of our cohort. HNA‐4 genotyping revealed no HNA‐4bb homozygous individuals. In contrast, HNA‐5bb homozygous individuals represented 2.43% of the population. Typing the HNA‐2 system for the single‐nucleotide polymorphism C42G showed that the C‐allele (69%) is overrepresented and is associated with an increased number of HNA‐2a–positive neutrophil subpopulations. CONCLUSION: This study describes for the first time the frequencies of all HNA systems, including the newly identified HNA‐3, within one cohort of Chinese Han population. Comparison with Caucasian populations may allow assessment of anti‐HNA alloimmunization and estimation of alloimmune neutropenia and TRALI incidence in Chinese populations.     

Genetic variants of human urea transporter-2 are associated with metabolic syndrome in Asian population

BackgroundA previous study has reported that the Ile227 and Ala357 genetic variants of human urea transporter-2 (HUT2) were associated with blood pressure in males in Asian population. In this study, we aimed to investigate five known HUT2 genetic variants with metabolic syndrome (MetS) and its related traits in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) study cohort.MethodsFive HUT2 single nucleotide polymorphisms (SNPs) were selected and genotyped among 1791 subjects in the SAPPHIRe study cohort. We first computed allele frequency and performed Hardy–Weinberg equilibrium (HWE) test in controls for each SNP. Next, we tested genotype associations with metabolic syndrome using multiple generalized estimating equations (GEE) models with covariate adjustment. Furthermore, multi-marker and multi-trait association tests were carried out using FBAT program. To account for multiple testing, Bonferroni correction was applied in this study.ResultsAmong those 5 HUT2 SNPs, SNPs 1, 2 and 3 were significantly associated with MetS in the total sample and females, separately (9 × 10^?4 ≤ p ≤ 0.04), but only the association between SNP 1 and MetS in females remained statistically significant after Bonferroni correction. When testing 5 SNPs simultaneously, significant associations were found with triglycerides (TG) (p = 0.04). Likewise, significant multi-trait association (combining the data of waist circumference, TG, high density lipoprotein (HDL) cholesterol and fasting glucose together) was found with SNP 2 (p = 0.04), but both results of multi-maker and multi-trait associations did not remain significant after multiple testing correction.ConclusionThe results have provided evidence that the HUT2 gene may play a certain role in developing MetS and its related traits in Asian population. Further investigation of the HUT2 gene influencing MetS and its related traits will be warranted.