The probability of HLA-C matching between patient and unrelated donor at the molecular level: estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles.

BACKGROUND: Recent evidence suggests a more significant role of HLA-C as a target of alloreactions after bone marrow transplantation than previously suspected. Although linkage disequilibrium (LD) between HLA-B and -C serogroups is well documented, the level of LD at the allelic level is not known. In this study, we determine the LD between HLA-B and -C alleles and estimate the probability of molecular HLA-C matching between unrelated individuals who match for both HLA-B alleles. METHODS: The study included 727 haplotypes from 849 individuals who were HLA-A, -B, -C and -DRB1 typed by high-resolution PCR-SSOP technique. Zelterman's statistic was used to test for global LD between HLA loci. LD between specific HLA-B and -C allelic combinations was calculated from their observed and expected frequencies in the study haplotypes. The probability of HLA-C matching for specific HLA-B allele was estimated from contingency table generated from the HLA-B and -C haplotypes. RESULTS: HLA-C was found to exist in LD with HLA-A and -B, as well as -DRB1, loci; however, it was strongest between HLA-B and -C loci. A marked variability in the level of LD between specific HLA-B and -C alleles was noticed. A strong LD was seen in some allele pairs like B*0702-C*w0702, B*3501-Cw*0401, and B*0801-Cw*0701. The overall estimated probability of HLA-C matching between unrelated individuals that match for both HLA-B alleles is 42.25%. For 237 (72.9%) of 325 combinations involving the 25 commonest HLA-B alleles, the estimated probability that the HLA-B-matched unrelated individuals will match for both HLA-C alleles is less than 50%. In addition, a 100% probability of matching for both HLA-C alleles is expected only if both individuals bear either B*0801/ B*0801 or B*4901/B*4901 or B*0801/B*4901. Probability tables for common alleles are presented. CONCLUSIONS: We conclude that, despite matching for both HLA-B alleles by high resolution DNA typing and the presence of a strong LD between HLA-B and HLA-C loci, unrelated individuals are more likely to mismatch rather than match for one or both HLA-C alleles.     

Anti-donor DR103 Immunization in a DRB1*0101 kidney allograft recipient

Posttransplant appearance of donor-specific anti-HLA antibodies is correlated with poor graft survival. Herein, we have provided evidence that an HLA-DRB1*0101 kidney allograft recipent developed anti-DR103 antibody after receiving a transplant from a HLA-DRB1*0103 cadaveric donor, resulting in graft loss. HLA-DRB1*0103 is a rare allele in Caucasian populations. It differs from DRB1*0101 only by three amino-acid substitutions and may play a central role in allorecognition. Nevertheless, our data showed that it induced alloimmunization in a DRB1*0101 recipient. Therefore, this new possibility of immunization must be taken into account before transplantation as well as after grafting.     

Human leukocyte antigen DRB1*04 is associated with rheumatoid arthritis in Kuwaiti patients

OBJECTIVES: Rheumatoid arthritis (RA) is a common, complex autoimmune disease known to be associated with inheritance of certain human leukocyte antigen (HLA)-DR alleles in different populations. This study investigated the association of DRB1 alleles in Kuwaiti patients with RA. MATERIALS AND METHODS: DRB1 alleles were analyzed in 47 Kuwaiti patients and 70 ethnically matched controls using a DNA-based sequence specific primer (SSP) method. RESULTS: The frequency of DRB1*04 allele was higher in patients compared to the controls (P < 0.012). The association with of HLA-DRB1*04 allele in our patients with RA was accounted for mainly by the seropositive group of patients (P < 0.05). Moreover, five patients were homozygous for DRB1*4 compared to none in the controls. None of the other DRB1 alleles tested was significantly higher in the patients. All patients homozygous for the DRB1*04 allele were females. There was no statistically significant difference in the frequency of DRB1*04 allele in patients classified according to presence of erosive disease or extra-articular manifestations. CONCLUSION: Our results indicate that in Kuwaiti patients, RA is associated with the presence of DRB1*04 allele. The lack of association with severity or the phenotype of RA is not surprising since this is a hospital-based study where patients tend to have a more severe disease.     

High resolution linkage and linkage disequilibrium analyses of chromosome 1p36 SNPs identify new positional candidate genes for low bone mineral density

Summary  A quantitative trait locus (QTL) for BMD maps to chromosome 1p36. We have analyzed a high density SNP panel from this region for linkage and association to BMD in 39 osteoporosis pedigrees. Our results support the presence of genes controlling BMD on 1p36 and indicate new candidates for further analyses. Introduction  Low BMD is one of the major risk factors for osteoporosis. Following a genome scan in a sample of Caucasian families recruited through probands with low BMD, a region on 1p36 near marker D1S214 received support as a QTL for BMD from linkage (maximum lod-score = 2.87) and linkage disequilibrium (LD) analysis (p < 0.01). Methods  To better characterize the genetic risk factors for low BMD located in this genomic region, we have genotyped the same group of families for 1095 SNPs located across 11 Mb on 1p36. Linkage and LD analyses have been performed using the variance component approach. Results  Multivariate linkage analysis indicated two QTLs for femoral neck BMD, lumbar spine BMD and trochanter BMD simultaneously on 1p36, with maximum lod-scores of 4.37 at 12 cM and 3.59 at 22 cM. LD analysis identified several SNPs potentially associated with BMD, including the RERE gene SNP rs11121179 (p  = 0.000005 for lumbar spine BMD). Other candidate genes include G1P2, SSU72 and CCDC27 (each containing 1 SNP with p < 0.001 for at least one BMD trait). Conclusions  This study supports the presence in 1p36 of QTLs affecting BMD at multiple skeletal sites. Replication of our results in other independent cohorts is warranted. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The connection between HLA microsatellites and HLA-B*27 gene in patients with psoriatic arthritis in Croatian population

The polymorphism at HLA microsatellites (D6S248, D6S2674, D6S2811 and D6S273) among patients with psoriatic arthritis (PsA) (N = 22) and healthy control subjects (K; N = 94), as well as haplotypic associations between tested loci were analysed in this study. All subjects were previously typed for HLA-A and -B by PCR-SSP method and were HLA-B*27 positive. HLA microsatellites were analysed using PCR-STR method and electrophoresis in an ALFexpress sequencer. The results demonstrated statistically significant P value for following alleles: D6S273-3 (PsA-21.1% vs. K-4.9%; P = 0.0013) and D6S273-4 (PsA-15.8% vs. K-32.1%; P = 0.0180). Analysis of haplotypic associations showed the only statistically significant difference for combination HLA-B*27/D6S273-4 (PsA-10.5% vs. K-40.2%; P = 0.0164). The results presented in this study lead to the assumption that some other gene/s involved in ethiology of PsA are located in the proximity of D6S273 microsatellite, but in order to reach a final conclusion, an increase in the number of patients is necessary.     

Patterns of linkage disequilibrium in the type 2 diabetes gene calpain-10

We investigated the patterns and extent of linkage disequilibrium (LD) in the vicinity of the type 2 diabetes gene calapin-10 (CAPN10) in Mexican Americans, European Americans, African Americans, and Chinese Americans. We found that CAPN10 occurs within a single block of high LD and that LD decays rapidly outside of the gene. This reduces the likelihood that associations between CAPN10 polymorphisms and type 2 diabetes could be attributed to variation at some distance from CAPN10. We also consistently observed that cases have more extensive LD than control subjects and that cases from families with evidence for linkage have more extensive LD than cases from families without evidence for linkage. These observations further suggest that there are one or more relatively common alleles increasing risk of type 2 diabetes in this local region.     

A study of HLA-G polymorphism and linkage disequilibrium in renal transplant patients and their donors

The role of the Major Histocompatibility Complex (MHC) in transplantation immunology is widely known. Incompatibilities associated with Human Leukocyte Antigens (HLA) between donors and recipients are related to poorer prognosis in allograft acceptance and survival, often resulting in rejection episodes. HLA-A, HLA-B, HLA-DR and HLA-DQ compatibility are widely studied in clinical transplants but few studies investigated the influence of non-classical HLA loci, such as HLA-G, a non-classical class I HLA gene located at 6p21.31 in the MHC region, i.e. 300 kb telomeric to HLA-A. MHC region genes are characterized by extreme polymorphism as well as strong positive linkage disequilibrium (LD) between HLA loci (alleles). LD studies related to MHC region provide investigators with a tool to assess candidate genes with an at-risk HLA haplotype, with implications for allograft transplants, human reproduction and disease susceptibility. Many studies reported striking LD between HLA-G and HLAA alleles and also between HLA-G and HLA Class II alleles, but the biologicalimplications for these findings are not clear yet. DNA sequencing methodology was used to determine HLA-G (exons 2 and 3) polymorphisms from 52 patients who underwent kidney transplantation and their donors. It is the purpose of this study to investigate the influence of HLA-G polymorphism in a set of kidney transplants and the occurrence of rejection episodes. It was observed that pairs with 2 HLA-G matches presented a lower risk of rejection occurrence than those pairs with 0 or 1 match. It was also observed that subjects whose genotype presented one synonymous substitution (S) in one HLA-G allele in the HLA-G0101 group of alleles and another allele with a non-synonymous substitution (N/S) on HLA-G0103, HLA-G010401, HLA-G010403 or HLA-G0105N alleles, apparently had a greater chance of rejection episodes. Additionally, HLA-G, as well as HLA-A, -B e -DR, compatibility may also be important for allograft acceptance (rejection probability lower than 0.09%). Besides, heterozygous S/NS patients had a five times greater chance of rejection than S/S and NS/NS patients. Some haplotypes found in the present study were already described in literature: A01-G01B (010102 or 0106), A03-G0101A, A23-G010401, A26-G01B, A31-G0103, A02-G0101A, A24-G0101A, A33-G0103, A68-G01B. We have also described LD between HLA-G alleles and HLA class II DRB1 allelic groups and found significant LD between DRB104-G01B, DRB113-G010401, DRB114-G010108, DRB115-G0103, DRB103-G0101A and DRB103-G01B.     

DRB1*15 allele is a risk factor for PR3-ANCA disease in African Americans

Anti-neutrophil cytoplasmic autoantibody (ANCA) disease rarely occurs in African Americans and risk factors for the disease in this population are unknown. Here, we genotyped MHC class II alleles and found that, among African Americans, those with proteinase 3-ANCA (PR3-ANCA) had 73.3-fold higher odds of having HLA-DRB1*15 alleles than community-based controls (OR 73.3; 95% CI 9.1 to 591). In addition, a disproportionate number of African American patients carried the DRB1*1501 allelic variant of Caucasian descent rather than the DRB1*1503 allelic variant of African descent. Among Caucasians, those with PR3-ANCA had 2.2-fold higher odds of carrying DRB1*1501 than controls (OR 2.2; 95% CI 1.2 to 4.0). A validation study supported by the Vasculitis Clinical Research Consortium confirmed the strong association between the DRB1*15 allele and PR3-ANCA disease, among African Americans. Furthermore, we found that DRB1*1501 protein binds with high affinity to amino acid sequences of sense-PR3, purportedly an antigenic epitope, and to the amino acid sequence complementary to this epitope in vitro. Peptides of sense-PR3 and complementary-PR3 also bound to TNF-α-induced surface expression of DRB1*1501 on peripheral neutrophils. Taken together, these data suggest HLA-DRB1*15 alleles contribute to the pathogenesis of PR3-ANCA disease.     

Acute Rejection of Hepatic Allografts From HLA-DR13 (Allele DRB1*1301)-Positive Donors

Acute rejection of hepatic allografts does not show consistent association with the number of mismatches of HLA classes I and II. Therefore, we investigated the relation between specific donor or recipient HLA antigens and the occurrence of acute rejection. HLA typing of 35 liver transplant recipients and donors was performed by serological standard technique, with confirmation and subtyping by polymerase chain reaction with sequence-specific primers. HLA class I antigens were not associated with the occurrence of acute rejection. The graft was positive for HLA-DR13 in 8 of 13 transplant recipients (62%) with acute rejection, but only 4 of 22 recipients (18%; P = .024;P_{Bonferroni-corrected} = .33, not significant) without rejection. The graft was positive for DRB1*1301 in 7 of 13 recipients (54%) with acute rejection, but only 1 of 22 recipients (5%) without rejection (P = .002; P_{Bonferroni-corrected} = .028). This patient had experienced long-lasting bacterial sepsis, which markedly reduced the risk for acute rejection. We speculate that the expression of donor DRB1*1301 (if mismatched) may increase the risk for acute hepatic allograft rejection. (Liver Transpl 2000;6:728-733.)     

The diversity of extended gene haplotypes HLA-B*27 in Croatia

In the present study the extended haplotypes of HLA-B*27 gene were analysed in the sample of 42 Croatian families. Peripheral blood (2 ml) was collected from all the individuals and genomic DNA was extracted using a commercial kit. The HLA alleles were determined using the method PCR sequence specific primers (PCR-SSP) while the microsatellite alleles were amplified using the method PCR-STR. Analysis of HLA-A-B*27-D6S2927-STR MICA-TNFalpha-DRB1 extended haplotypes demonstrated the strongest linkage disequilibrium between HLA-B*27 alleles and microsatellite alleles D6S2927-1 and STR_MICA-A4. Analysis indicated that the rare allele B*2730 is always present in the extended haplotype HLA-A3-B*2730-D6S2927-1-STR MICA-A4-TNFalpha-9-DRB1*16. The results of the present study will be applied in future studies of association between microsatellite alleles and spondyloarthropathies and contribute to a better understanding of peptide binding to HLA class I molecules, as well as other aspects of immune response.     

Next Generation Sequencing Reveals the Association of DRB3*02:02 With Type 1 Diabetes

The primary associations of the HLA class II genes, HLA-DRB1 and HLA-DQB1, and the class I genes, HLA-A and HLA-B, with type 1 diabetes (T1D) are well established. However, the role of polymorphism at the HLA-DRB3, HLA-DRB4, and HLA-DRB5 loci remains unclear. In two separate studies, one of 500 subjects and 500 control subjects and one of 366 DRB1*03:01–positive samples from selected multiplex T1D families, we used Roche 454 sequencing with Conexio Genomics ASSIGN ATF 454 HLA genotyping software analysis to analyze sequence variation at these three HLA-DRB loci. Association analyses were performed on the two HLA-DRB loci haplotypes (DRB1-DRB3, -DRB4, or -DRB5). Three common HLA-DRB3 alleles (*01:01, *02:02, *03:01) were observed. DRB1*03:01 haplotypes carrying DRB3*02:02 conferred a higher T1D risk than did DRB1*03:01 haplotypes carrying DRB3*01:01 in DRB1*03:01/*03:01 homozygotes with two DRB3*01:01 alleles (odds ratio [OR] 3.4 [95% CI 1.46–8.09]), compared with those carrying one or two DRB3*02:02 alleles (OR 25.5 [3.43–189.2]) (P = 0.033). For DRB1*03:01/*04:01 heterozygotes, however, the HLA-DRB3 allele did not significantly modify the T1D risk of the DRB1*03:01 haplotype (OR 7.7 for *02:02; 6.8 for *01:01). These observations were confirmed by sequence analysis of HLA-DRB3 exon 2 in a targeted replication study of 281 informative T1D family members and 86 affected family-based association control (AFBAC) haplotypes. The frequency of DRB3*02:02 was 42.9% in the DRB1*03:01/*03:01 patients and 27.6% in the DRB1*03:01/*04 (P = 0.005) compared with 22.6% in AFBAC DRB1*03:01 chromosomes (P = 0.001). Analysis of T1D-associated alleles at other HLA loci (HLA-A, HLA-B, and HLA-DPB1) on DRB1*03:01 haplotypes suggests that DRB3*02:02 on the DRB1*03:01 haplotype can contribute to T1D risk.The Type 1 Diabetes Genetics Consortium (T1DGC) (1) is an international collaboration that has collected thousands of multiplex family samples, as well as case and control samples, and has carried out linkage and association analysis for genome-wide single nucleotide polymorphisms (SNPs), candidate gene SNPs, and major histocompatibility complex (MHC) SNPs, as well as for alleles and haplotypes at the highly polymorphic HLA class I and class II genes (2–7). More than 40 different loci have been associated with T1D (3); however, linkage and association analyses have identified the HLA region as the major genetic determinant of T1D risk. The most strongly T1D-associated MHC markers are defined by the HLA-DRB1, -DQA1, and -DQB1 haplotypes (4), although alleles at other HLA loci, notably HLA-A and HLA-B, as well as HLA DPB1 (5–11) and other non-HLA loci across the genome, also contribute to T1D risk (3).Although the association of HLA-DRB1 alleles with T1D is well established, the role of polymorphism at the HLA-DRB3, HLA-DRB4, and HLA-DRB5 loci has been studied less frequently, partly due to technical issues in genotyping. Most high-resolution genotyping strategies for HLA-DRB1 depend on DRB1-specific PCR primers to minimize confounding signals from coamplified secondary DRB loci. All copies of chromosome 6 have a DRB1 locus, and most, but not all, have a functional second DRB locus. This second DRB locus is DRB3 for DRB1*03, *11, *12, *13, and *14 haplotypes, DRB4 for DRB1*04, *07, and *09 haplotypes, and DRB5 for DRB1*15 and *16 haplotypes. DRB1*01, DRB1*08, and DRB1*10 haplotypes do not have a second DRB locus.The clonal sequencing property of next generation sequencing systems, such as the Roche 454 GS FLX and GS Junior Systems, allows the use of generic DRB primers to coamplify and sequence exon 2 from DRB1, DRB3, DRB4, and DRB5 loci (12–14). We have used the Roche 454 amplicon sequencing system with “fusion primers” containing the 454 adaptor (A and B) sequences and 10 base multiplex ID tags (MIDs) to amplify and sequence exon 2 from different individuals (13,14). The genotyping software consolidates these clonal sequence readings, sorts them to individual DRB loci and to individual samples, and compares them to the IMGT/HLA Sequence Database to assign specific genotypes at the HLA-DRB1, HLA-DRB3, HLA-DRB4, and HLA-DRB5 loci.To assess the potential role of these secondary HLA-DRB loci in T1D, association analyses were carried out at the two DRB locus haplotype levels, focusing on the DRB1*03:01 haplotypes bearing DRB3*01:01 or DRB3*02:02. The role of HLA-DRB3 polymorphism in T1D risk was initially evaluated in a case/control study and then examined in a targeted replication study of informative patients from multiplex HLA-genotyped families, allowing analysis of HLA haplotypes and the potential role of T1D-associated alleles at other HLA loci.     

HLA-DQB1 and DRB1 alleles in Egyptian children with steroid-sensitive nephrotic syndrome

Steroid-sensitive nephrotic syndrome (SSNS) of children has been associated with several HLA-DR and DQ alleles. To investigate this association in Egyptian children, 27 patients with SSNS were typed for HLA-DRB1 and DQB1 alleles using DNA polymerase chain-reverse hybridization technique. The results were compared with 121 healthy subjects for HLA-DRB1 and 59 subjects for DQB1 alleles. We found that: (1) patients have higher frequencies of both DQB1 ^* 0601 (81.5% vs. 10.2% in controls, Pc = 0.0001) and DRB1 ^* 01 (44.4% vs. 3.3% in controls, Pc = 0.00003). Their relative risks are significantly high [38.9, confidence interval (CI) = 10.7–140.7, and 23.4, CI=6.7–81.9, respectively]; (2) the frequency of DRB1 ^* 11 alleles was low in SSNS patients (3.75% vs. 32.2% in controls), but was not significant when P was corrected (P = 0.005, Pc = NS). These findings suggest that DQB1 ^* 0601 and DRB1 ^* 01 or closely associated unknown genes confer susceptibility to SSNS. However, further studies with larger numbers of patients are needed. Received June 27, 1997; received in revised form October 23, 1997; accepted October 26, 1997     

Distribution of HLA-B*27 subtypes in Tunisians and their association with ankylosing spondylitis

ObjectiveThe human leukocyte antigen HLA-B27 is a class I antigen of the major histocompatibility complex strongly associated with ankylosing spondylitis (AS) and other related spondyloarthropathies (SpAs). The mechanism of this association remains unknown. HLA-B27 is a serologic specificity that represents a family of at least 25 different HLA-B27 alleles (2701–2725). These alleles are closely related by nucleotide sequence homology, but differ in ethnic distribution. The purpose of the present study is to investigate the distribution of HLA-B27 alleles in healthy controls and in patients with ankylosing spondylitis (AS).MethodsWe selected 160 HLA-B27-positive individuals (39 controls and 121 patients with ankylosing spondylitis). Typing of HLA-B27, and Cw alleles were performed by polymerase chain reaction amplification with sequence specific primers (PCR–SSP), and by serological typing (microlymphocytotoxicity).ResultsSeven B27 subtypes were identified: B*2702, 03, 04, 05, 07, 09 and B*2714. The distribution of these alleles in the population of patients was B*2702 (47.1%) and B*2705 (47.1%). These subtypes were also detected in 16 (41%) and 16 (41%), respectively of the 39 control subjects. HLA-B*2707 was detected in 4 (3.31%) patients and in 3 (7.6%) controls. B*2704, 09 and B*2714 were relatively rare and were detected in one subject each. No significant differences were noticed in the frequencies and distribution of HLA-B27 alleles between patients and controls.ConclusionsOur results show a restricted number of HLA B27 subtypes associated with AS. B*2702 and B*2705 were equally common in patients and controls. The most prominent B27/Cw haplotypes in the patient groups and controls were B*2702/Cw02022 and B*2705/Cw02022.     

Presence of the human leukocyte antigen class II gene DRB1*1101 predicts interferon gamma levels and disease recurrence in melanoma patients

Background Increased interferon γ (IFN-γ) levels are an independent predictor of melanoma recurrence. Human leukocyte antigen (HLA) class II genes can regulate cytokine production; we investigated whether these genes would predict IFN-γ levels and recurrence in melanoma patients. Methods Of 591 patients who presented with localized melanoma, 579 underwent identification of HLA class II alleles; 233 melanoma patients and 90 controls underwent determination of plasma IFN-γ levels. HLA class II genes were examined for association with IFN-γ levels and disease recurrence. Results After a median follow-up of 60 months, melanoma patients with IFN-γ levels above the mean control value were more likely to have developed disease recurrence compared with patients with levels below the mean. The HLA class II geneHLA-DRB1*1101 was the strongest predictor of recurrence, andHLA-DRB1*1101-positive melanoma patients had increased levels of IFN-γ compared with patients lacking the gene. Conclusions Among patients with localized melanoma, bothHLA-DRB1*1101 and increased IFN-γ levels were associated with an increased risk for recurrence;HLA-DRB1*1101-positive patients had relatively increased levels of IFN-γ. HLA class II genes may mediate cytokine production in melanoma patients, and this mechanism may help determine the risk of disease recurrence. Presented at the 53rd annual meeting of the Society of Surgical Oncology, Washington, DC, March 16, 2001.     

HLA-B27与强直性脊柱炎的相关性研究进展

背景 强直性脊柱炎(ankylosing spondylitis,AS)是一种常见的自身免疫性关节病,好发于年轻男性,该疾病目前早期诊断较闲难,治疗效果不理想,以往研究表明HLA-B27与AS有很强的相关性,90%左右的AS患者HLA-B27呈阳性,但是仍有10%的患者HLA-B27呈阴性,值得临床进一步研究.目的 现...     

Linkage and linkage disequilibrium mapping of genes influencing human obesity in chromosome region 7q22.1-7q35

Linkage results suggest that the region of chromosome 7 containing the leptin gene cosegregates with extreme obesity; however, leptin coding region mutations are rare. To investigate whether the leptin flanking sequence and/or a larger 40-cM region (7q22.1-7q35) contributes to obesity, we genotyped individuals from 200 European American families segregating extreme obesity and normal weight (1,020 subjects) using 21 microsatellite markers and two single nucleotide polymorphisms (SNPs) and conducted nonparametric linkage (NPL) analyses. We also carried out transmission disequilibrium tests for 135 European American triads using 27 markers (including eight SNPs). Both quantitative (MERLIN-regress) and qualitative (GENEHUNTER and MERLIN-npl) analyses provided evidence for linkage for BMI (GENEHUNTER NPL = 2.98, 20 cM centromeric to leptin at the marker D7S692; MERLIN Z score = 3.56). Results for several other regions in 7q gave weak linkage. Transmission disequilibrium test (TDT) and quantitative TDT (and quantitative pedigree disequilibrium test) analyses suggest linkage disequilibrium near leptin and other regions of 7q. Our results suggested that there could be two or more genes in chromosome region 7q22.1-7q35 that influence obesity. A new region found by this study (D7S692-D7S523, 7q31.1) has the most consistent linkage results and could harbor obesity-related genes.     

西北高原汉族人群人类白细胞抗原-A、B、DRB1基因多态性与慢性肾衰竭相关性分析

目的：研究西北高原汉族人群人类白细胞抗原(human leukocyte antigen,HLA)-A、B、DRB1基因多态性与慢性肾脏疾病(chronic kidney disease,CKD)的相关性。方法选择410例等待肾移植的CKD患者和403例健康个体作为研究对象,且所有研究对象均来自中国西北高原地区并在当地生活多年。采用序列特异引物聚合酶链式反应技术对研究对象进行基因分型,比较两个群体HLA-A、HLA-B和 HLA-DRB1基因频率的差异,并采用相对风险系数评价 HLA与CKD的相关性。结果与健康对照组比较,CKD 组 HLA-A?32(2.43%比0.37%,P=0.001;odds ratio [OR]=6.692,confidence interval [CI]：1.981~22.608)、HLA-A?68(2.07%比0.37%,P=0.002;OR=5.667,CI：1.654~19.412)和HLA-DRB1?16(3.41%比0.87%,P=0.001;OR=4.035;CI：1.753~9.292)具有高频率,而HLA-B?14(0.36%比1.48%,P=0.02;OR=0.243;CI：0.068~0.864)却频率较低。结论西北汉族人群中,HLA-A?32、HLA-A?68和 HLA-DRB1?16可能是 CKD 的易感基因,而HLA-B?14则可能是保护性基因。