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At least 379 records · Page 21Linked to original sources
PubMed2002

Angiotensinogen M235T gene polymorphism and recurrent restenosis after repeated percutaneous transluminal coronary angiography.

The present study was designed to prospectively test the hypothesis that gene polymorphisms of the renin-angiotensin system are associated with recurrent restenosis after repeated percutaneous transluminal coronary angioplasty. Five hundred and eleven patients after first successful angioplasty were characterized with respect to the angiotensinogen M235T, angiotensin-converting enzyme insertion/deletion and angiotensin II type 1 receptor A1166C gene polymorphisms. In 164 of these patients repeated angioplasty on a restenotic lesion was performed. After repeated angioplasty, 46 patients had recurrent restenosis as defined by a greater than 50% progression of residual stenosis. In the recurrent restenosis group there was a statistically significant higher percentage of patients receiving cholesterol-lowering drugs compared with the group of patients without recurrent restenosis. The two groups of patients did not differ with respect to procedural and angiographic parameters. There were significantly more carriers of the angiotensinogen 235T allele in the recurrent restenosis group than in the control group without recurrent restenosis. No differences between the two groups were found with respect to the other gene polymorphisms investigated. According to the results of a multifactorial analysis of variance, only the 235T allele of the angiotensinogen gene and not cholesterol drug therapy independently affected the increase of stenosis at follow-up angiography. In conclusion, the angiotensinogen 235T allele may be an independent predictor for recurrent restenosis after repeated angioplasty.

Adult↗
PubMed2001

Association of HLA-DR genotypes and IL-1ra gene polymorphism with treatment failure of budesonide and disease patterns in Crohn's disease.

OBJECTIVE: Associations between HLA-DR genotypes and susceptibility to Crohn's disease (CD) have been reported. However, it is not known whether certain HLA-DR genotypes or IL-1ra gene polymorphism are associated with responsiveness to treatment or different clinical patterns of disease. DESIGN/SETTING: In a large, randomized, controlled multicentre trial, 318 patients with CD were treated with daily doses of 6, 9 or 18 mg budesonide. Patients were stratified into two groups: patients without steroid pretreatment and with active CD (CDAI > 150) and patients with conventional steroid pretreatment of < or= 30 mg prednisolone per day, which was replaced by oral budesonide within 3 weeks. MAIN OUTCOME MEASURES: The HLA-DRB1 genotypes 1-16 and the IL-1ra gene polymorphism were examined for an association with budesonide treatment failure. RESULTS: Only HLA-DR 8 was associated with treatment failure of budesonide. HLA-DR 8 is not very common. Only 17/243 patients who could be evaluated expressed this genotype, and 13 of these 17 patients did not respond to budesonide (P < 0.00067). Neither the other HLA-DR genotypes nor the IL-1ra gene polymorphism had an influence on treatment outcome of budesonide therapy. No significant association of fistulas, perianal disease, need for bowel resections, and disease localization with certain HLA-DRB1 genotypes or the IL-1ra gene polymorphism were found. CONCLUSIONS: This is the first description of an association of a certain HLA-DR genotype (HLA-DR 8) with treatment failure in inflammatory bowel disease (IBD).

Adult↗
PubMed2001

Platelet glycoprotein gene polymorphisms and risk of thrombosis: facts and fancies.

Over the past several years, platelet glycoprotein gene polymorphisms have received increasing attention as possible inherited determinants of prothrombotic tendency. However, their role in genetic susceptibility to thrombotic disease remains controversial. The glycoprotein IIIa Leu33Pro amino acid substitution appears to be associated with a subtle effect on platelet thrombogenicity in vitro, but is not a major risk factor for arterial thrombotic disease among the general population. Evidence suggests that the glycoprotein IIIa Pro33 allele may be associated with increased risk of thrombotic events following coronary re-vascularization and possibly among younger subjects with atherosclerosis. The nucleotide 807T variant of glycoprotein Ia is associated with increased platelet glycoprotein Ia/IIa receptor density, collagen-induced platelet adhesion and an increased risk of early onset myocardial infarction and stroke. Evaluation of the roles of the glycoprotein Ibalpha Thr145Met and variable number of tandem repeat polymorphisms has been complicated by their lack of well-defined effects on platelet adhesive function and the strong linkage disequilibrium between the two sites. Future epidemiologic studies of platelet glycoprotein gene polymorphisms will require larger sample sizes and family based approaches to further elucidate clinically important associations with thrombotic disease, including gene-environment and gene-gene interactions. Other polymorphisms of potential functional significance within genes encoding platelet membrane proteins will undoubtedly be discovered. The challenge will be to integrate advances in platelet biology with molecular and genetic epidemiology to enhance our understanding of the genetic determinants of common, but etiologically complex thrombotic diseases.

Epidemiologic Studies↗
PubMed1997

MUC6 gene polymorphism in healthy individuals and in gastric cancer patients from northern Portugal.

Mucins exhibit a high degree of genetic polymorphism because of the presence of a variable number of tandem repeats. The aims of this work were to describe the MUC6 gene polymorphism in the Portuguese population and to evaluate whether MUC6 gene polymorphism was involved in individual susceptibility to gastric cancer development, as observed previously for the MUC1 gene. We found that the 10 alleles identified in the population of blood donors (n = 376), by Southern blot analysis, were also found in gastric cancer patients (n = 157). However, significant differences in allelic frequencies between the two populations were observed for 4 of the 10 alleles, in agreement with those described previously for the MUC1 gene; the largest allele was more frequent in blood donors, and smaller alleles were more frequent in gastric cancer patients. Our results suggest that MUC6 gene polymorphism is involved in the predisposition to gastric carcinoma development.

Adult↗
PubMed2007

The IL1A (-889) gene polymorphism is associated with chronic periodontal disease in a sample of Brazilian individuals.

BACKGROUND AND OBJECTIVE: It has been proposed that genotypes reflective of polymorphisms in cytokine genes can predispose individuals to disease by enhancing inflammatory processes. The C/T polymorphism at position -889 of the IL1A gene influences interleukin-1alpha expression, with the T allele inducing higher expression. The aim of this study was to evaluate the association of the IL1A (-889) gene polymorphism in Brazilian individuals with different clinical forms of periodontitis and severity of disease. MATERIAL AND METHODS: DNA was obtained from oral swabs of 163 Brazilian individuals and was amplified using the polymerase chain reaction (PCR). Products were submitted to digestion and were analyzed by electrophoresis to distinguish the C and T alleles. RESULTS: A significant difference in the genotype distribution was observed when comparing the chronic periodontitis group with the control group, evaluating only nonsmokers (chi-squared analysis = 9.91; p = 0.007), as well as when smokers were included (chi-squared analysis = 6.36; p = 0.04). Moreover, we observed a higher incidence of the T allele in the chronic periodontitis group (37.8%) when compared with the control group (18.4%) in nonsmokers (p = 0.006, odds ratio = 2.69, confidence interval = 1.27-5.68) and also when smokers were included (p = 0.03, odds ratio = 1.87, confidence interval = 0.98-3.56). No statistical difference was observed when the aggressive periodontitis group was compared with the control group. With regard to severity of disease, no statistical difference was observed. CONCLUSION: These data show an association of the IL1A (-889) polymorphism with chronic periodontitis in Brazilian individuals.

Adolescent↗
PubMedDate not supplied

Apolipoprotein E gene polymorphism effects triglycerides but not CAD risk in Caucasian women younger than 65 years.

The pathogenesis of CAD is similar in man and woman, yet some risk factors have a greater impact on the CAD risk in woman than in man. In this study we assessed the effect of the apoE gene polymorphism on lipid metabolism and risk for CAD in women younger than 65 years (premature CAD). In a cross-sectional case-control study, 147 female Caucasian patients with premature CAD (confirmed by coronarography) were compared with a control group of 114 healthy Caucasian women. The apoE allele frequencies of patients vs. controls were 5.1% vs. 5.7% for 2, 85.4% vs. 83.3% for 3, and 9.5% vs. 11% for epsilon4. The subjects with epsilon2/3 genotype had statistically significantly higher triglycerides levels than the subjects with epsilon3/3 genotype (2.23 +/- 2.13 mmol.L(-1) vs. 1.73 +/- 0.84 mmol.L(-1); p<0.05). Logistic regression analysis revealed no association between risk genotypes (3/4 and 4/4) of the apoE gene polymorphism and CAD risk (OR 0.9; 95% CI 0. 5-1.7, P=0.7). We observed metabolic clustering of diabetes mellitus, arterial hypertension, higher BMI and triglycerides, and lower HDL cholesterol in the CAD group compared to the control group. Arterial hypertension, diabetes, HDL cholesterol level, and BMI were independent risk factors for premature CAD in female population, whereas, the risk genotype of the apoE gene polymorphism was not. In conclusion, in Slovene women risk genotypes of the apoE gene polymorphism are not associated with premature CAD; a metabolic clustering of diabetes, HDL, triglycerides and arterial hypertension is frequently present in Caucasian women with premature CAD.

Apolipoproteins E↗
PubMed2006

Association between dopamine D4 receptor (DRD4) gene polymorphisms and novelty-elicited auditory event-related potentials in preschool children.

We investigated associations of the exon III repeat and the -521 C/T polymorphisms of the DRD4 gene with novelty-elicited auditory ERP components and behavioral resistance to distraction in 57 healthy, typically developing 6-year-old children. Dopamine-related gene polymorphisms have previously been linked to processes directing focused attention. We did not find associations between the 7-repeat allele or the T.7 haplotype and the early ERP responses suggesting that DRD4 polymorphisms did not affect the detection of novelty. However, the same polymorphisms affected the late negative components (LN1 and LN2). Late negativities elicited by deviant and novel sounds have been regarded as reflecting reorientation after distraction or additional processing of new information. Children carrying the T.7 haplotype had significantly smaller LN1 and LN2 amplitudes. The presence of the T.7 haplotype also significantly enhanced behavioral resistance to distraction. We suggest that less distraction in T.7 carriers led to less reorienting activity (reflected by the LN components). We also speculate that activation of less sensitive and fewer D4 receptors (as with the T.7 haplotype) is less effective in modulating GABAergic inhibitory signaling, which in turn is reflected in smaller LN amplitudes.

Acoustic Stimulation↗
PubMed2003

Angiotensinogen gene polymorphism, plasma angiotensinogen, and risk of hypertension and ischemic heart disease: a meta-analysis.

OBJECTIVE: The aim of this study was to investigate whether the M235T polymorphism in the angiotensinogen gene was associated with angiotensinogen levels, systolic and diastolic blood pressure, hypertension, and risk of ischemic cardiovascular disease in different ethnic populations. METHODS AND RESULTS: One hundred twenty-seven studies published between January 1992 and March 2002 examining the association of angiotensinogen gene polymorphisms with the above-mentioned end points were selected. Pooled effect sizes and Mantel-Haenszel odds ratios were calculated using Review Manager. In white subjects, genotype was associated with a stepwise increase in plasma angiotensinogen levels of 5% (95% CI, 2% to 8%; P=0.0004) in MT heterozygotes and 11% (7% to 15%; P<0.00001) in TT homozygotes compared with MM individuals. Correspondingly, genotype was associated with a stepwise increase in aggregated odds ratio for hypertension of 1.08 (95% CI, 1.01 to 1.15) in MT individuals and 1.19 (1.10 to 1.30) in TT individuals in white subjects and of 1.29 (95% CI, 0.96 to 1.74) and 1.60 (1.19 to 2.15) in Asian subjects. M235T genotype did not predict systolic or diastolic blood pressure or risk of ischemic heart disease or myocardial infarction in either ethnic group. CONCLUSIONS: Angiotensinogen M235T genotype was associated with a stepwise increase in angiotensinogen levels in white subjects and a corresponding increase in risk of hypertension in both white and Asian subjects.

Angiotensinogen↗
PubMed1998

Bronchial responsiveness and angiotensin-converting enzyme gene polymorphism in sarcoidosis patients.

BACKGROUND: Angiotensin-converting enzyme (ACE) inactivates bradykinin and tachykinins, which are potent bronchoconstrictors and mediators of inflammatory reactions. It has recently been shown that an insertion (I)/deletion (D) polymorphism in the ACE gene accounts for variation in serum ACE level. We investigated bronchial responsiveness in patients with sarcoidosis to determine whether it might be associated with ACE gene polymorphism. SUBJECTS: Bronchial responsiveness was assessed in 21 patients with sarcoidosis, 21 patients with asthma, and 18 healthy control subjects. ACE polymorphism was also examined in the 21 patients with sarcoidosis. METHODS: Bronchial responsiveness was measured by recording respiratory resistance with continuous inhalation of methacholine from 49 to 25,000 microg/mL in concentration. The ACE genotype was determined using the polymerase chain reaction. RESULTS: We found a significant increase in bronchial responsiveness in sarcoidosis patients as compared with healthy control subjects (p<0.01). In the sarcoidosis group, patients with the II genotype demonstrated significantly more coughing (p<0.05) and a greater bronchial responsiveness (p<0.05) than did those with DI or DD genotypes. CONCLUSION: Patients with sarcoidosis have increased bronchial responsiveness to some extent, the degree apparently depending on the ACE genotype.

Adult↗
PubMed2001

[Association of apolipoprotein E gene polymorphism with early-onset coronary heart disease and its effect on plasma lipid levels].

OBJECTIVE: To detect the association of apolipoprotein E(apoE) gene polymorphism with early-onset coronary heart disease(CHD) and to evaluate the effect of apoE gene polymorphism on plasma lipid levels. METHODS: The apoE genotypes of 52 early-onset CHD patients (aged 38-55 years), 161 aged CHD patients and 180 controls were determined by PCR-RFLP. Plasma lipid levels were measured by using routine methods. RESULTS: Five genotypes of apoE, E3/3, E4/4, E3/2, E4/3 and E4/2 were detected in this study. Statistically differences in apoE4/3 and epsilon4 frequencies between early-onset and aged CHD patients and controls were seen (P<0.05). The frequency of epsilon4 in the early-onset CHD patients was higher than that in the aged CHD patients. epsilon4 and epsilon2 alleles also differently affected the plasma total cholesterol and low density lipoprotein cholesterol levels. CONCLUSION: These results suggest that apoE gene polymorphism is in association with the occurrence and development of early-onset CHD and it affects the plasma lipid levels.

Adult↗
PubMed2006

Human serum paraoxonase gene polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.

OBJECTIVES: It has been reported that human serum paraoxonase (PON1) gene is associated with coronary heart disease (CHD) and diabetes mellitus (DM). However, little is known about the role of PON1 gene polymorphism in cerebral infarction (CI). For this, we have investigated the relationship between PON1 gene polymorphisms, Q192R and L55M, and CI in Chinese Han population. METHODS: The PON1 genotypes, Q192R and L55M, from 153 CI patients and 153 healthy individuals, were determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Their allele frequencies were then determined. The association of the PON1 gene polymorphism with the risk of CI was analysed by statistical analysis software. RESULTS: The frequencies of PON1-Q192R genotypes in CI and control group are 13.7 and 9.8% (QQ), 51.6 and 53.6% (QR), 34.6 and 36.6% (RR) respectively. There is no significant difference in PON1-Q192R genotype (p=0.566) and allele frequencies (p=0.505) between CI patients and controls. The frequencies of PON1-55 genotypes in the CI and control group are 96.7 and 93.5% (LL), 3.3 and 6.5% (LM) respectively. No MM genotype was found in both CI and control group. No significant difference in genotype (p=0.289) and allele (p=0.296) distribution between CI patients and controls was observed. DISCUSSION: Our results suggest that the human serum paraoxonase polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population.

Adult↗
PubMed2002

Methylenetetrahydrofolate reductase gene polymorphism, hyperhomocysteinemia and occlusive retinal vascular disease in type 2 diabetic and non-diabetic subjects.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphism may cause hyperhomocysteinemia, which affects the vascular endothelium and may induce occlusive vascular disease (OVD). Hypertension thickens small-sized arterial walls and attenuates intramural blood flow. Such OVD can be studied in retinal angiograms as a decrease in the arterio-venous ratio (AVR). Diabetes, by altering microvascular structure and function, in many ways modifies this AVR. OBJECTIVE: To assess whether MTHFR gene polymorphism (C677T) by causing hyperhomocysteinemia affects the retinal AVR in type 2 diabetic and non-diabetic subjects. METHODS: Eighty-four recently diagnosed (< 1 year) type 2 diabetic and 115 non-diabetic subjects were included in the study. Retinal fluoresceine angiograms were recorded and the mean AVR was calculated by measuring transverse vessel diameters at 6 locations. The mean AVR was used as a marker of OVD. The MTHFR VV, VA and AA genotypes were determined by PCR and plasma homocysteine by high-pressure liquid chromatography. RESULTS: In the diabetic subjects with the VV, VA and AA genotypes, the plasma homocysteine levels were 16.5 +/- 7, 12.5 +/- 4.6 and 11.3 +/- 4.9 microM, respectively (p = 0.008, ANCOVA). The corresponding values in controls were 14.6 +/- 3.8, 13.7 +/- 5.7 and 11.6 +/- 4.4 (p = 0.08). Correspondingly, in the diabetic subjects, the AVR values were 0.71 +/- 0.07, 0.75 +/- 0.07 and 0.73 +/- 0.1 (p = NS, ANOVA) and in the control subjects they were 0.8 +/- 0.14, 0.81 +/- 0.12 and 0.76 +/- 0.09 (p = NS, ANOVA). Multiple linear regression analysis (best model chi2 = 18.2, R2 = 0.10, p < 0.001) showed that AVR was related to diastolic blood pressure (t = -3.7, p < 0.001) and GFR (t = -2.2, p = 0.03). There was no relation between the AVR and plasma homocysteine levels. CONCLUSION: In the present study of recently diagnosed type 2 diabetic and non-diabetic subjects, MTHFR gene polymorphism (C677T mutation) slightly affected the plasma homocysteine level but did not alter the arterio-venous ratio.

Adult↗
PubMed2001

Gene polymorphisms and transplantation.

The influence of gene polymorphisms in key immunoregulatory molecules on the clinical course post-transplant has become an area of active research, since it offers a possible explanation for the heterogeneity in outcomes between individuals. Several groups have now investigated the association of polymorphisms in molecules--including cytokines, cytokine receptors, adhesion molecules and costimulatory molecules--that participate in the immune response to an allograft. Several interesting observations have been made that would suggest that genetic variability influencing allograft survival reaches beyond that of the MHC molecules.

Gene Expression Regulation↗
PubMed2002

[Influence of cytokine gene polymorphism on renal transplantation].

OBJECTIVE: To study the influence of cytokine gene polymorphism on the incidence of acute rejection in renal transplantation. METHODS: The cytokine genotypes of TNF-alpha, TGF-beta(1), IL-10 and IL-6 in 24 normal people and 115 consecutive renal transplant recipients were determined by PCR-SSP using sequence-specific oligonucleotide primer. The cytokine genotypes were then correlated with the incidence of acute rejection in renal transplantation. RESULTS: The frequency of TNF-alpha and IL-10 low producer genotype in the 115 kidney recipients and control group was 88.7%, 80% and 87.5%, 75% respectively, and the frequency of TGF-beta(1) and IL-6 high producer genotype was 79.1%, 100% and 66.7%, 100% respectively. The incidence of acute rejection was higher in the recipients with TNF-(high producer or IL-10 intermediate high producer genotype than in the recipients with low producer genotype [53.8%, 43.5% vs 18.6% (chi(2) = 8.17), 17.4% (chi(2) = 7.16), P < 0.01, respectively]. CONCLUSION: This study demonstrated that TNF-alpha and IL-10 gene polymorphism has significant influence on the incidence of acute rejection in renal transplantation.

Adolescent↗
PubMed2004

Gene-environment interaction in hyperkinetic conduct disorder (HD + CD) as indicated by season of birth variations in dopamine receptor (DRD4) gene polymorphism.

Recently, an interaction between season of birth and the expression of candidate genes has been suggested. Season of birth variations in tryptophan hydroxylase (TPH), the serotonin transporter (5-HTTLPR) and the dopamine D4 receptor (DRD4) gene polymorphisms are different for affective disorders and schizophrenia. The DRD4 gene has been postulated as a candidate gene for attention-deficit-hyperactivity disorder (ADHD), equivalent to hyperkinetic disorder (HD). The seven-repeat long variant of this gene (DRD4*7) in comparison to the short repeat variants of the DRD4 gene polymorphism, has been found to be associated with ADHD. A seasonal pattern of birth has also been proposed for different subtypes of ADHD. Therefore, in a subgroup of children with HD and conduct disorder (CD) and in healthy controls, we investigated a possible association between the DRD4*7 allele and HD + CD in association with the season of birth. Supporting this hypothesis, we found an interaction between the seasons of birth and the expression of the DRD4 candidate gene in children with HD + CD as well as in controls, which differ significantly from each other. Depending on the season of birth, children carrying the DRD4*7R allele showed different relative risks for developing HD + CD.

Adolescent↗
PubMedDate not supplied

Effects of ACE gene polymorphism on vitamin D therapy according to parathyroid hormone level in patients on hemodialysis.

Medical management is still far from optimal in secondary hyperparathyroidism. This may be explained, at least in part, by genetic differences. The aim of this study was to evaluate the association of genetic influences of angiotensinconverting enzyme (ACE) gene polymorphisms with response to vitamin D therapy among patients on hemodialysis (HD). Eighty-two patients (female/male, 34/48; mean age, 47.5+/-15.3 y; HD duration time, 76.6+/-33.2 mo) with endstage renal disease who were on maintenance HD were included in the study. Five-year retrospective demographic, clinical, laboratory, and treatment data (5-y cumulative doses of phosphate-binding drugs and oral and intravenous cumulative doses of active vitamin D) were retrieved from patients' hospital records. ACE gene polymorphisms of patients were documented and were used to group patients as follows: The insertion/deletion polymorphism group (I/D) consisted of (1) group non-DD (n=43), who had the DI or II allele, and (2) group DD (n=39), who had the DD allele. Patients with the DD allele (group DD) of ACE gene polymorphism had (1) significantly elevated mean 5-y intact parathyroid hormone levels when compared with the non-DD group (P=.009), and (2) significantly elevated oral and intravenous 5-y cumulative doses of vitamin D. Oral and intravenous 5-y cumulative doses of vitamin D used in group DD patients were significantly higher than those in group I patients (P=.038 and P=.037, respectively). Knowledge of genetic differences among patients on HD may be useful to the clinician in planning treatment strategy. ACE gene polymorphism may have an effect on hyperparathyroidism, as is seen in patients on HD. Patients from this group who have resistant hyperparathyroidism may be candidates for ACE inhibitor therapy.

Female↗
PubMed1995

Human T-cell receptor V beta gene polymorphism and multiple sclerosis.

Population-based genetic associations have been reported between RFLPs detected with probes corresponding to the genes encoding the beta chain of the T-cell receptor for antigen (TCRB) and a variety of autoimmune disorders. In the case of multiple sclerosis (MS), these studies have localized a putative disease-associated gene to a region of approximately 110 kb in length, located within the TCRB locus. In the current study, all 14 known TCRBV (variable region) genes within the region of localization were mapped and identified. The nucleotide sequences of these genes were determined in a panel of six MS patients and six healthy controls, who were human-leukocyte antigen and TCRB-RFLP haplotype matched. Nine of the 14 TCRBV genes studied showed evidence of polymorphism. PCR-based assays for each of these polymorphic genes were developed, and allele and genotype frequencies were determined in a panel of DNA samples from 48 MS patients and 60 control individuals. No significant differences in allele, genotype, or phenotype frequencies were observed between the MS patients and controls for any of the 14 TCRBV-gene polymorphisms studied. In light of the extensive linkage disequilibrium across the region studied, the saturating numbers of polymorphisms examined, and the direct sequence analysis of all BV genes in the region, these results suggest that it is unlikely that germ-line polymorphism in the TCRBV locus makes a major contribution to MS susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2002

Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation.

We made the hypothesis that donor and recipient gene polymorphisms that drive the host response to microorganisms could be associated with infections after bone marrow transplantation (BMT). HLA-identical BMT was performed for patients with acute (n = 39) or chronic leukemia (n = 68). Genotyping was performed in 107 D/R DNA pairs for gene polymorphisms of cytokines (tumor necrosis factor-alpha [TNF-alpha] and TNF-beta, interleukin-1 receptor antagonist [IL-1Ra], IL-6, and IL-10), adhesion molecules (CD31 and CD54), Fcgammareceptors (FcgammaRIIa, IIIa, IIIb), mannose-binding lectin (MBL), and myeloperoxidase (MPO). First infection (overall) and first episodes of bacterial, viral, or invasive fungal infection were studied retrospectively for 180 days after BMT. Univariate and multivariate analyses, using death as a competing event, were performed to study risk factors. In multivariate analysis, first overall infections were increased in patients with the FcgammaRIIa R-131 genotype (hazard ratio [HR] = 1.92; P =.04), and severe bacterial infections were increased when the MPO donor genotype was AG or AA (HR = 2.16; P =.03). Viral and invasive fungal infections were not influenced by any genetic factor studied. Interestingly, we also found that (1) time to neutrophil recovery was shorter when donors were FcgammaRIIIb HNA-1a/HNA-1b (HR = 1.77; P =.002); (2) donor IL-1Ra (absence of IL-1RN*2) increased the risk for acute graft-versus-host disease (GVHD) (II-IV) (HR = 2.17; P =.017); and (3) recipient IL-10 (GG) and IL-1Ra genotypes increased the risk for chronic GVHD (P =.03 and P =.03, respectively). Finally, 180-day transplantation-related mortality rates were increased when donors were FcgammaRIIIb HNA-1a/HNA-1a or HNA-1b/HNA-1b (HR = 2.57; P =.05) and donor MPO genotype was AA (HR = 5.14; P =.004). In conclusion, donor and recipient gene polymorphisms are informative genetic risk factors for selecting donor/recipient pairs and could help in the understanding of mechanisms involved in host defenses of BM transplant recipients.

Adolescent↗