Chronic norovirus infection in primary immune deficiency disorders: an international case series.

OBJECTIVE: Predictive factors associated with clinical outcomes of chronic norovirus infection (CNI) in primary immunodeficiency diseases (PIDD) are lacking. METHOD: We sought to characterize CNI using a multi-institutional cohort of patients with PIDD and CNI using the Clinical Immunology Society's CIS-PIDD Listserv e-mail group. RESULTS: Thirty-four subjects (21 males and 13 females) were reported from centers across North America, Europe, and Asia. All subjects were receiving high doses (median IgG dose: 1200 mg/kg/month) of supplemental immunoglobulin therapy. Fifty-three percent had a complete absence of B cells (median B-cell count 0; range 0-139 cells/µL). Common Variable Immune Deficiency (CVID) subjects manifested a unique phenotype with B-cell lymphopenia, non O+ blood type, and villous atrophy (logistic regression model, P = 0.01). Five subjects died, all of whom had no evidence of villous atrophy. CONCLUSION: While Norovirus (NoV) is thought to replicate in B cells, in this PIDD cohort of CNI, B-cell lymphopenia was common, indicating that the presence of B lymphocytes is not essential for CNI.

Clinical Value of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Response Evaluation after Primary Treatment of Advanced Epithelial Ovarian Cancer.

AIMS: To prospectively evaluate the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the definition of the treatment response after primary treatment of advanced epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Forty-nine patients with advanced EOC had an 18F-FDG PET/CT scan before and after primary treatment. The treatment response was defined with the currently used radiological and serological Response Criteria in Solid Tumors (RECIST1.1/GCIC) criteria and the modified PET Response Criteria in Solid Tumors (PERCIST). The concordance of the two methods was analysed. If the patient had a complete response to primary treatment by conventional criteria, the end of treatment 18F-FDG PET/CT scan (etPET/CT) was not opened until retrospectively at the time of disease progression. The ability of etPET/CT to predict the time to disease recurrence was analysed. The recurrence patterns were observed with an 18F-FDG PET/CT at the first relapse. RESULTS: The agreement of the RECIST1.1/GCIC and modified PERCIST criteria in defining the primary treatment response in the whole patient cohort was good (weighted kappa coefficient = 0.78). Of the complete responders (n = 28), 34% had metabolically active lesions present in the etPET/CT, most typically in the lymph nodes. The same anatomical sites tended to activate at disease relapse, but were seldom the only site of relapse. In patients with widespread intra-abdominal carsinosis at diagnosis, the definition of metabolic response was challenging due to problems in distinguishing the physiological FDG accumulation in the bowel loops from the residual tumour in the same area. The presence of metabolically active lesions in the etPET/CT did not predict earlier disease relapse in the complete responders. CONCLUSIONS: In the present study, etPET/CT revealed metabolically active lesions in complete responders after EOC primary therapy, but they were insignificant for the patient's prognosis. The current study does not favour routine use of 18F-FDG PET/CT after EOC primary treatment for complete responders.

Systematic Screening of Adverse Reactions to Metal Debris after Recap-M2A-Magnum Metal-on-Metal Total Hip Arthroplasty.

BACKGROUND AND AIMS: An adverse reaction to metal debris is a known complication after large diameter head metal-on-metal total hip arthroplasty. However, the failure rate varies depending on the implant design. Therefore, we investigated the prevalence of adverse reaction to metal debris, as well as the symptoms and risk factors after undergoing a ReCap-M2a-Magnum large diameter head metal-on-metal total hip arthroplasty. MATERIALS AND METHODS: Between 2005 and 2012, 1188 patients (1329 hips) underwent ReCap-M2a-Magnum total hip arthroplasty at our institution. Systematic screening for adverse reaction to metal debris was arranged using the Oxford Hip Score questionnaire, hip and pelvic radiographs, and assessments of the serum chromium and cobalt ion levels. Clinical evaluation and magnetic resonance imaging were performed for the symptomatic patients, as well as those with either chromium or cobalt ion levels ⩾5 µg/L. The prevalence of adverse reaction to metal debris after ReCap-M2a-Magnum total hip arthroplasty was assessed, and the risk factors for adverse reaction to metal debris were evaluated using logistic regression. The mean follow-up time was 5.2 (0.003-9.1) years. This study was an extension of a previous study conducted at our institution with 80 patients. RESULTS: In total, 33 patients (33 hips, 2.5% of all hips) required a revision operation due to adverse reaction to metal debris. Moreover, 157 hips exhibited definitive adverse reaction to metal debris, but a revision operation was not performed (157 of 1329 hips, 11.8% of all hips). Overall, 190 out of 1329 (14.3%) hips had definitive adverse reaction to metal debris. Pain, subluxation sensation, clicking, swelling, a small head size, and a fair/poor Oxford Hip Score were associated with definitive adverse reaction to metal debris. CONCLUSION: We found a high prevalence of adverse reaction to metal debris in the ReCap-M2a-Magnum total hip arthroplasty patients in this study; however, most of the patients did not require revision operations.

Freedom Constrained Liner for the Treatment and Prevention of Dislocation in Total Hip Arthroplasty.

BACKGROUND AND PURPOSE: Dislocation is one of the most common complications following total hip arthroplasty. The aim of our study was to assess failure rate of the Biomet Freedom constrained liner (Biomet, Warsaw, IN, USA) either in revision surgery for recurrent dislocation, or as a preventive method in high dislocation risk patients. PATIENTS AND METHODS: We assessed retrospectively 105 consecutive surgical procedures in 103 patients where a Freedom constrained liner or cup was used in Turku University Hospital over a 7-year period from 2007 to 2014. The mechanical failure rate of the device was assessed based on medical records. The average age of the patients was 73.4 years. The number of male patients was 53 (51%). Mean follow-up time was 2.5 years. The association between failure of the device and potential risk factors-age, gender, indication, and approach-was analyzed with logistic regression. Results were expressed by odd ratios and 95% confidence intervals. RESULTS: The mechanical failure rate of the Freedom device was 6 out of 105 (5.7%). None of the 11 preventive primary THAs against dislocation failed, 4 out of 52 (7.7%) preventive revision THAs against dislocation failed, and 2 out of 42 (4.8%) of the treated dislocation cases failed. Four out of six failures were dislocations due to impingement and failure of the locking mechanism. Two liners failed because of loosening. The risk factors assessed were not associated with failure of the device. INTERPRETATION: We found out that the mechanical failure rate of a Freedom constrained device was low. These results encourage us to continue using the device.

Whole body PET/CT in the follow-up of asymptomatic patients with stage IIB-IIIB cutaneous melanoma.

BACKGROUND: Whole body positron emission tomography (PET)/computed tomography (CT) is a sensitive imaging technique in patients with metastatic melanoma, but its role in the follow-up of asymptomatic high-risk patients is unclear. The aim was to study the role of PET/CT as a routine surveillance imaging tool in asymptomatic high-risk patients at the early stage of follow-up combined with a sufficient follow-up over several years. MATERIAL AND METHODS: A total of 110 asymptomatic patients with clinically local American Joint Committee on Cancer (AJCC) stage IIB-IIIB melanoma underwent routine whole body PET/CT scanning after a mean interval of seven months after initial surgery. Clinical data were retrospectively analyzed after a median follow-up time of 4.6 years. RESULTS: Recurrent melanoma was detected in 45 patients (41%) and 36 (33%) died of melanoma. In 11 asymptomatic patients (10%) occult disease was detected with a single PET/CT. In seven of these patients (64%), positive PET/CT finding had major influence in treatment decisions. Four patients underwent surgical metastasectomy and two of them remained disease-free. In 34 patients (31%) PET/CT revealed no disease, but recurrence was detected at a median time of 19 months after negative PET/CT scan. In 50 patients (45%) PET/CT finding was true negative. In 15 patients (14%) scan was false positive leading to additional management or repetitive imagings. CONCLUSION: A single PET/CT could detect 24% of all recurrences in asymptomatic melanoma patients at the early stage of follow-up, but an earlier detection of occult metastases did not improve survival.

Acetabular reconstruction with impaction bone grafting and cemented polyethylene socket in total hip revision arthroplasty.

BACKGROUND AND AIMS: Bone deficiency in revision total hip arthroplasty is a challenge to the surgeon. One option for restoration of the bone stock is impaction bone grafting and use of a cemented socket. The aim of this study was to evaluate the mid-term clinical outcome of impaction bone grafting and cemented socket revisions. MATERIAL AND METHODS: A total of 59 patients (60 hips) underwent revision arthroplasty with impaction bone grafting and application of a cemented socket on the acetabular side in the Turku University Hospital from 1999 to 2004. The study end-point was re-revision for any reason. The cumulative percentages for survival were followed and estimated with Kaplan-Meier curves. Associations between occurrence of re-revision and potential risk factors were analyzed with logistic regression. Results were quantified by odd ratios and 95% confidence intervals. The mean age of the patients was 69 years (33% male). A total of 3% of the patients had a class I Paprosky acetabular defect, 38% had class II, and 55% had class III. RESULTS: The overall survival rate was 73%. The mean follow-up time was 7 years. The most common reason for re-revision was aseptic loosening of the acetabular component (13 patients, 81% of re-revisions). Cox's regression analysis did not identify any risk factors for re-revision. CONCLUSION: Our results were inferior compared to some previous studies. Impaction bone grafting of acetabular defects in revision total hip arthroplasty may not always provide a reliable bone stock in long-term.

Risk of donor-site lymphatic vessel dysfunction after microvascular lymph node transfer.

BACKGROUND: Microvascular lymph node transfer has been used to improve lymphatic function in patients with lymphoedema. We previously reported changes in the lymphatic function of the donor limb after lymph node transfer. For this reason, we modified our surgical method to be more conservative. SUBJECTS AND METHODS: Microvascular lymph node transfer was performed in 13 patients using the previously reported original method. Sixteen patients were operated upon using the more conservative modified method. Lymphatic function in the donor limb was evaluated using volumetry, lymphoscintigraphy and tissue water percentage. RESULTS: In the original method group, the donor-limb volume was on average greater (199 ± 540 ml) than in the non-operated control limb. The volume difference between the limbs was smaller (151 ± 463 ml) in the modified method group. Two patients in the original method group had abnormal transport index (Ti) values in lymphoscintigraphy indicating decreased lymphatic function of the donor limb. In the modified method group, the Ti-values remained normal. The tissue water percentage of the donor limb was on average 40% ± 4% in the original method group and 40% ± 3% in the modified method group. Importantly, none of the patients in either group developed clinical lymphoedema in the donor limb during the 11-84-month follow-up. CONCLUSIONS: Even with the more conservative lymph node transfer method, we can observe slight, subclinical signs of lymphatic dysfunction in the donor limb. These results highlight the importance of minimizing the surgical exploration in the inguinal area and avoiding damage to the lymphatic vessels or sentinel nodes draining the lower limb.

Experience of structural onlay allografts for the treatment of bone deficiency in revision total hip arthroplasty.

BACKGROUND AND AIMS: Loss of femoral bone stock in elective revision total hip arthroplasty poses unique and substantial challenges. Structural onlay allografts may provide mechanical stability for the cementless revision prosthesis and increase bone stock. MATERIAL AND METHODS: At least one cortical onlay allograft was used in 40 elective total hip arthroplasty revisions (40 patients) to reconstruct femoral bone defects. The operations were performed between January 1999 and August 2010 in the Turku University Hospital, Finland. The mean follow-up time was 52 months (range: 12-125 months). RESULTS: The allografts were incorporated into the bone tissue in 37 of 40 (92.5%) patients. Cementless revision stems healed in 36 of 40 (90.0%) patients, but these patients were not exactly the same patients whose allografts were successfully incorporated. One or more surgical complications were experienced by 14 of 40 (35.0%) patients during follow-up. In all, 4 of 40 (10.0%) patients (all women) had hip infections during follow-up. Of the 7 patients with rheumatoid arthritis, 4 (57.1%) had at least one complication. CONCLUSIONS: The use of the cortical onlay allografts provides a feasible option for restoring the integrity of the proximal femur in revision total hip arthroplasty, but the complication rate is high, particularly in female patients with rheumatoid arthritis.

Early results of large head metal-on-metal hip arthroplasties.

BACKGROUND AND AIMS: Total hip arthroplasty significantly improves patient's life quality. However, total joint replacement is associated with possible complications, such as dislocations, infections, fractures and periprosthetic osteolysis. The goal of this study was to evaluate a large head metal-on-metal total hip arthroplasties and analyse short term complications related to them. MATERIAL AND METHODS: Between 9/2005 and 6/2009, a total of 691 hip replacements were performed on 635 patients with the use of Magnum M2 large head cementless metal-on-metal prosthesis in Turku University Hospital. All patients had a scheduled follow-up at two to three months, and at one year. The results were evaluated using X-rays, Harris Hip Score (HHS), and evaluating post-operative complications and reasons for re-operations. RESULTS: During our follow-up the HHS median raised from its preoperative value of 59.8 to 86.4 two to three months after the operation, and to 93.9 one year after the operation. As a complication we had five infections requiring single open debridement (early infection) or a two stage revision. Seven patients had a periprosthetic femoral fracture that was operated and 11 patients were reoperated because of acetabular component malposition, fracture or early loosening. We did not observe any dislocations, n. ischiadicus damages, squeeking or complications related to high metal ion release (ALVAL-reactions (Aseptic Lymphocyte-dominated Vasculitis-Associated Lesion) or pseudotumours). CONCLUSIONS: The metal-on-metal bearing pair allows large femoral head size, which decreases the risk for dislocation. It may also decrease the risk for osteolysis and aseptic loosening in a long run. Early complication rate related to the bearing surface is minimal. Metal-on-metal prosthesis is a good choice for young and active patients with good bone quality.

Sentinel lymph node biopsy and survival in elderly patients with cutaneous melanoma.

BACKGROUND: Sentinel lymph node biopsy (SNB) is a widely adopted staging procedure in patients with cutaneous melanoma. The benefits of SNB have not been evaluated thoroughly in older age groups. METHODS: This was a two-centre retrospective observational study of patients with melanoma aged at least 70 years undergoing SNB. RESULTS: A total of 423 patients were included. SNB was successful in 405 patients (95·7 per cent), of whom 88 (21·7 per cent) had sentinel node metastasis. During a median follow-up of 2·5 years, recurrence developed in 80 patients (18·9 per cent). Nodal recurrence developed in eight sentinel node-negative patients, giving a false-negative rate of 8·3 per cent, a sensitivity of 91·7 per cent and an overall diagnostic accuracy of 98·0 per cent. A total of 46 patients (10·9 per cent) died from melanoma and 42 (9·9 per cent) from other causes. At 5 years, the relapse-free survival rate was 80·0 per cent in sentinel node-negative patients and 39 per cent in node-positive patients; cancer-specific survival rates were 88·6 per cent and 46 per cent respectively (P < 0·001). In multivariable analysis, sentinel node metastasis (P < 0·001), a Breslow thickness of at least 2·0 mm (P = 0·007) and presence of ulceration (P = 0·012) were independent prognostic factors for cancer-specific survival. CONCLUSION: SNB is a feasible and accurate technique for detecting nodal metastases in older patients with melanoma. Sentinel node status is the most important predictor of cancer-specific outcome in the elderly.

Up to 10 years follow up of the use of 71 cortical allografts (strut-grafts) for the treatment of periprosthetic fractures.

BACKGROUND AND AIMS: Periprosthetic fractures are often located in areas of poor bone quality. There are multiple strategies to manage these fractures. Stable fixation in areas of low bone quality may require the use of cortical bone strut allografts. MATERIAL AND METHODS: Cortical allograft struts were used in the treatment of 71 patients with periprosthetic fractures between a 10 year period from 1/1999 until 12/2008. 18 patients had a periprosthetic fracture around the knee implant, 52 around the hip implant and 1 in between the hip and knee prosthesis. The average follow-up time was 943 days ranging from 90 days to 3428 days. RESULTS AND CONCLUSIONS: The overall union rate was 91%. 20 patients died during the follow-up, 6 of them during the first six month after operation. 8 patients (12%) had an diagnosed infection during the follow-up time. The specific strategy chosen to periprosthetic fracture treatment should depend on the quality of the remaining bone stock, type of the implant, location and classification of the fracture and on patients related factors, such age age and comorbidities. Use of cortical bone struts is a good option in fractures associated with poor bone quality. Use of allograft strut combined with a nonlocking plate, which offers the highest stiffness known, may provide superior bio-mechanical stability compared with other methods in some situations.

Selenium protects sorghum leaves from oxidative damage under high temperature stress by enhancing antioxidant defense system.

Oxidative stress is commonly induced when plants are grown under high temperature (HT) stress conditions. Selenium often acts as an antioxidant in plants; however, its role under HT-induced oxidative stress is not definite. We hypothesize that selenium application can partly alleviate HT-induced oxidative stress and negative impacts of HT on physiology, growth and yield of grain sorghum [Sorghum bicolor (L.) Moench]. Objectives of this study were to investigate the effects of selenium on (a) leaf photosynthesis, membrane stability and antioxidant enzymes activity and (b) grain yield and yield components of grain sorghum plants grown under HT stress in controlled environments. Plants were grown under optimal temperature (OT; 32/22°C daytime maximum/nighttime minimum) from sowing to 63 days after sowing (DAS). All plants were foliar sprayed with sodium selenate (75mgL(-1)) at 63 DAS, and HT stress (40/30°C) was imposed from 65 DAS through maturity. Data on physiological, biochemical and yield traits were measured. High temperature stress decreased chlorophyll content, chlorophyll a fluorescence, photosynthetic rate and antioxidant enzyme activities and increased oxidant production and membrane damage. Decreased antioxidant defense under HT stress resulted in lower grain yield compared with OT. Application of selenium decreased membrane damage by enhancing antioxidant defense resulting in higher grain yield. The increase in antioxidant enzyme activities and decrease in reactive oxygen species (ROS) content by selenium was greater in HT than in OT. The present study suggests that selenium can play a protective role during HT stress by enhancing the antioxidant defense system.

Clinical PET imaging of insulinoma and beta-cell hyperplasia.

Persistent hyperinsulinemic hypoglycemia (PHH) is caused by solitary benign insulinoma or hyperplasia of pancreatic beta cells. In infants, PHH is caused by functionally defective hyperplastic beta cells, which are either diffusely or focally distributed in the pancreas. In adults, insulinoma is the most common cause of PHH, but recently, an increasing number of beta-cell hyperplasias has been reported among adults. The cause of adult beta-cell hyperplasia is not known. Whether the increased use of bariatric surgery in the treatment of severe obesity plays a role here is under investigation. Accurate localization of disease focus in both insulinoma and focal beta-cell hyperplasia provides an important support for surgery, especially as the use of laparoscopic surgery has increased. Conventional imaging of these challenging pancreatic lesions has evolved during recent years, but current imaging methods still lack sufficient sensitivity or are invasive. In most pancreatic NETs, the usefulness of positron emission tomography (PET) with fluorine-labeled fluorodeoxyglucose ([(18)F]FDG) for lesion detection is limited because of the low glucose turnover of these tumors. Based on the capacity of pancreatic beta cells to take up and decarboxylate amine precursors, several investigators have studied patients with pancreatic NETs using aminoacid precursors, such as [(18)F]dihydroxyphenylalanine (DOPA) and [(11)C]hydroxytryptophan (5-HTP), in an attempt to increase the sensitivity of PET scanning. Another characteristic of NETs is the expression of somatostatin receptors, and thus encouraging studies with somatostatin receptor imaging with [(18)Ga]-labeled somatostatin analogs have emerged as a new interesting imaging tool for the diagnosis of pancreatic NETs. This article provides an overview of our experiences and the current literature on PET imaging in patients with PHH caused by insulinoma or beta-cell hyperplasia.

Imaging of tumor hypoxia to predict treatment sensitivity.

Non-invasive detection of tumor hypoxia using radiolabeled 2-nitroimidazoles has been a major effort during the last two decades. Recent years have witnessed the introduction of several new compounds which are chemically related to [(18)F]fluoromisonidazole (FMISO) but show slight but distinct differences in biodistribution and metabolic clearance. Although [(18)F]FMISO has shown clinical potential it suffers from suboptimal oxygen dependent tissue contrast and newer agents seek to improve this essential feature. The limited data on other interesting tracers keeps the investigators busy at demonstrating the potential advantages over [(18)F]FMISO while efforts should start to concentrate on proving the clinical significance of such techniques in the form of outcome data from image-guided therapy modification. We review here our experiences with two hypoxia-avid agents [(18)F]fluoroerythronitromidazole (FETNIM) and [(18)F] 2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) and focus on the similarities and differences of these two tracers in comparison to other radiolabeled 2-nitroimidazoles. It is recognized that only [(18)F]FMISO has thus far shown clinical utility and newer tracers need to be tested against this circumstance.

Lymphotoxin alpha LTA+496C allele is a risk factor for periodontitis in patients with coronary artery disease.

Periodontitis and coronary artery disease (CAD) are inflammatory diseases and associated with each other. The major histocompatibility complex (MHC) region carries genes involved in immune response and inflammation. We investigated whether the MHC genes correlate with the presence of periodontitis or with the occurrence of periodontal pathogens in patients with CAD. Blood and saliva samples from CAD patients (n = 106) were collected at the time of hospitalization. Nine MHC genetic markers [human leukocyte antigen (HLA)-A, HLA-B, HLA-DRB1, lymphotoxin alpha (LTA) +253(a/g), +496(C/T), +633(c/g), +724(C/A), C4A and C4B)] were typed. Based on panoramic tomography, patients were categorized into nonperiodontitis and periodontitis groups. Two major periodontal pathogens, Aggregatibacter (Actinobacillus) actinomycetemcomitans and Porphyromonas gingivalis, were cultivated and polymerase chain reaction-amplified from salivary samples. Serum immunoglobulin (Ig)A and IgG antibody levels to these pathogens were measured. In the univariate analysis, LTA+496C allele (OR = 5.29; 95% CI = 2.07-13.51, P = 0.00027), and the occurrence of P. gingivalis in saliva (OR = 4.74; 95% CI = 1.64-13.70; P = 0.002) were more frequent in periodontitis when compared with nonperiodontitis. Similarly, serum IgA antibody level against the pathogen was increased in periodontitis (P = 0.048). In the multiple logistic regression analysis, when a wide range of covariates was included, the LTA+496C allele (OR = 10.87; 95% CI = 3.23-36.60; P = 0.00012) and the elevated serum IgA antibody level against P. gingivalis (OR = 1.56; 95% CI = 1.05-2.30; P = 0.026) remained as significant risk factors for periodontitis. In conclusion, the major finding of this study is that the LTA+496C allele is associated with periodontitis in patients with CAD.

Complement and c4 null alleles in severe chronic adult periodontitis.

Severe forms of chronic periodontitis affect up to 10% of adults. Tumour necrosis factor and lymphotoxin-alpha genes in the major histocompatibility complex are associated with severe periodontitis. Complement factor C4 is a nearby, polymorphic, functionally relevant gene region. Although associated with chronic mucosal infections, C4 deficiencies have not been assessed in adult periodontitis patients. We tested whether complement levels are systemically altered and C4 deficiencies associated with severe chronic periodontitis. In a case-control study, we analysed levels of plasma C3, and C4, serum classical pathway haemolytic activity, C4 allotypes and C4 gene numbers in 37 patients with severe chronic periodontitis and in 150 voluntary controls. Plasma levels of C3 were higher, and classical pathway haemolytic activity was lower in patients than in controls. Partial C4 gene deficiencies were more frequent in patients than in controls (odds ratio 2.4, 95% confidence interval 1.1-5.5, P = 0.032). Changes in complement levels may reflect chronic, recurring inflammation. C4 gene deficiencies are associated with predisposition to chronic periodontitis.

Human MHC region harbors both susceptibility and protective haplotypes for coronary artery disease.

Aiming to study the role of human major histocompatibility complex (MHC) region on coronary artery disease (CAD), we enrolled two separate patient materials and controls. First, heart transplantation recipients (n = 276) were divided into three subgroups according to the severity of atherosclerosis. The human leukocyte antigen (HLA)-A-B-DR haplotype and gene frequencies were compared between groups. Second, patients with acute coronary syndrome (ACS) (n = 100) and healthy controls (n = 74) were assessed by nine genetic MHC markers (HLA-A, HLA-B, HLA-DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and the frequencies were compared. In the heart transplantation recipients, HLA-DR1 was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37; 95% confidence interval (CI) 1.33-4.25; P = 0.003]. Similarly, in the patients with ACS, HLA-DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95% CI 1.25-4.44; P = 0.007). HLA-DRB1*01 was associated with low-density-lipoprotein cholesterol (OR 5.32; 95% CI 1.64-17.26; P = 0.005) and smoking habit (OR 3.13; 95% CI 1.09-9.03; P = 0.035) as risk factors. The strongest protective gene was HLA-B*07 alone (OR 0.46; 95% CI 0.24-0.88; P = 0.02) or together with the haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001). In conclusion, human MHC region harbors genes that protect from and predispose to CAD.