Potential influence of interleukin-1 haplotype IL-1 beta-511*T-IL-1RN*1 in conferring low risk to middle third location of esophageal cancer: a case-control study

Interleukin (IL)-1 gene polymorphisms affect several inflammatory diseases, including cancer. Therefore, we studied genetic association of biallelic (-511C>T) polymorphism of IL-1β and 86-bp VNTR polymorphism of IL-1RN in 159 patients with esophageal cancer (EC) and 194 age- and gender-matched healthy controls. Genetic analysis for IL-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of IL-1β (-511C>T) and IL-1RN (variable number tandem repeat) genotypes, alleles, and haplotypes did not differ significantly between patients and controls. However, IL-1β -511TT genotype and T1+ haplotype combination illustrated low risk for disease at the middle third location of the tumor (odds ratio [OR] = 0.27; 95% confidence interval [CI] = 0.11–0.62; p = 0.002; OR = 0.462; 95% CI = 0.253–0.845, p = 0.01). In conclusion, subjects with IL-1β -511TT genotype or IL-1β*T-IL-1RN*1 (T1) haplotype had lower risk for middle third tumor location of EC in a northern Indian population.     

Genetic susceptibility to rheumatic heart disease and streptococcal pharyngitis: association with HLA-DR alleles

Acute rheumatic fever (ARF) is a systemic inflammatory disease that develops as a consequence of an exaggerated immune response to group A beta-haemolytic streptococci, which causes pharyngitis. Major manifestations of ARF include carditis, arthritis and chorea. Several investigators have attempted to establish a relation between ARF and human leucocyte antigens (HLA). Heterogeneity in various studies has been found, although associations with certain antigens were reported. The aim of this study was to analyse whether HLA-DR alleles play a role in the resistance or susceptibility to streptococci-related disorders including rheumatic heart disease (RHD) as a sequela of ARF and recurrent streptococcal pharyngitis in Turkish patients. The study included 102 patients with RHD, 71 persons with recurrent streptococcal pharyngitis and 130 healthy controls. HLA-DR alleles were typed by using polymerase chain reaction (PCR)-sequence-specific primers. Positive association with HLA-DRB1*07 allele was found for RHD when compared with healthy controls [29.4% vs 13.1%; P < 0.01, P-corrected: P < 0.01, odds ratio (OR) 2.78, 95% confidence interval (CI) 1.43-5.26] and also for recurrent streptococcal pharyngitis (26.8% vs 13.1%; P < 0.05, P-corrected: P < 0.05, OR 2.44, 95% CI 1.17-3.56). The frequency of HLA-DRB1*11 allele was decreased in patients with RHD (23.5% vs 42.3%; P < 0.01, P-corrected: P < 0.01, OR 0.42, 95% CI 0.24-0.75). Data suggest that HLA-DRB1*07 allele may be a genetic factor in increasing the susceptibility to develop RHD and recurrent streptococcal pharyngitis. HLA-DRB1*11 allele seems to be a protective factor against RHD.     

Lack of association between Helicobacter pylori infection with dupA-positive strains and gastroduodenal diseases in Brazilian patients

Duodenal ulcer-promoting gene (dupA) was recently described as a new putative Helicobacter pylori virulence marker associated with an increased risk for duodenal ulcer and reduced risk for gastric carcinoma in Japan and Korea. Since differences regarding the association among H. pylori markers and H. pylori-associated diseases have been demonstrated around the world, we evaluated the presence of the gene in 482 strains from Brazilian children (34 with duodenal ulcer and 97 with gastritis) and adults (126 with duodenal ulcer, 144 with gastritis and 81 with gastric carcinoma) by PCR using the described primers and an additional set of primers based on Brazilian strain sequences. The results were confirmed by sequencing. The presence of cagA was investigated by PCR and also included in the analysis. dupA was present in 445 (92.32%) and absent in 29 (6.02%) strains. All samples from children with and without duodenal ulcer were dupA-positive (p=1.0). No association was observed among the strains from adults with gastritis (92.36%), duodenal ulcer (87.30%, p=0.30) and gastric carcinoma (87.65%, p=0.31). Conversely, cagA-positve status remained independently associated with duodenal ulcer (children: odds ratios (OR)=5.58, 95% confidence intervals (CI)=1.67–18.50; adults: OR=3.33, 95% CI=2.14–5.19) and gastric carcinoma (OR=6.58, 95% CI=3.51–12.30) in multivariate analyses. The presence of dupA was significantly higher in strains from children than in those from adults (p=0.01). In conclusion, dupA is highly frequent and not associated with H. pylori-associated diseases in both Brazilian adults and children, which points to regional differences in the distribution of the gene.     

Significantly increased levels of mannose-binding lectin (MBL) in rheumatic heart disease: a beneficial role for MBL deficiency

Although mannose-binding lectin (MBL) is known to be involved in the primary defense against microorganisms, there are emerging lines of evidence for an active proinflammatory role for MBL in different chronic diseases. In this study we determined the circulating levels of MBL in patients with rheumatic heart disease (RHD). A total of 100 patients (77 women, 23 men; mean age 45.8 +/- 11 years, range 19-76 years) with chronic RHD, and a previous diagnosis of rheumatic fever, were studied. Transthoracic echocardiography was performed in all patients to evaluate valvular heart disease. Ninety-nine healthy individuals matched for age, sex and ethnic origin were included as controls. MBL concentration was measured by enzyme-linked immunosorbent assay and C3 and C4 levels by turbidimetry. MBL levels were significantly higher in patients with RHD than in healthy subjects (mean +/- SEM: 3036.2 +/- 298.9 ng/ml versus 1942.6 +/- 185.5 ng/ml, P <0.003). In addition, MBL deficiency was more prevalent in controls (17.1%) than in patients (9% P <0.09). Concentrations of C4 were within the normal range (22.7 +/- 0.8 mg/dl, normal: 10.0-40.0 mg/dl), while C3 concentrations were found to be elevated (109.2 +/- 3.6 mg/dl, normal: 50.0-90.0 mg/dl). No correlation was observed between serum MBL levels and valve area or the type of surgical procedure. The significantly elevated circulating MBL levels in patients with RHD together with the greater prevalence of MBL deficiency in controls suggest that MBL may cause undesirable complement activation contributing to the pathogenesis of RHD.     

Alleles of the IL12B 3'UTR associate with late onset of type 1 diabetes

Carriage of a polymorphism in the 3′untranslated region of the IL12B gene encoding IL-12p40 was investigated in subjects with type 1 diabetes mellitus stratified by age at diagnosis (n = 648) and compared with a population-based control cohort (n = 246) residing in Western Australia. DNA samples were genotyped by polymerase chain reaction-restriction fragment length polymorphism or pyrosequencing. The C allele was more common in patients diagnosed after age 16 years than in controls (29% vs 17%, OR = 2.0, 95% CI = 1.4–2.7, p = 0.00003) or than in patients diagnosed when younger age 16 years (29% vs 22%, OR = 1.4, 95% CI = 1.1–1.9, p = 0.01). This reflected increases in homozygous and heterozygous carriage of the C allele. Heterozygosity was associated with a delayed disease in the late-onset diabetics (p = 0.005; Student’s t-test). The effects of IL12B 3′untranslated region alleles on type 1 diabetes mellitus may reflect different levels of p40 available to form p40 homodimer, IL-12 (p35p40), and IL-23 (p19p40).     

Effects of cyclin D1 (CCND1) polymorphism on susceptibility to lung cancer in a North Indian population

Cyclin D1 is involved in normal regulation of the cell cycle and plays an important role in the transition from G1 to S phase of the cell cycle. The CCND1 gene has a G→A polymorphism in exon 4 that increases the frequency of alternate splicing. We analyzed the potential role of CCND1 gene polymorphisms in lung cancer patients (n = 151) and in a matched control population (n = 151). DNA was isolated from blood samples, and exon 4 of CCND1 was amplified by polymerase chain reaction. After digestion with MspI, common CCND1 polymorphic alleles were analyzed by means of agarose gel electrophoresis. The data obtained were analyzed using multiple logistic regression. After adjustment for age, sex, and smoking status, the AG genotype was associated with an increased risk for overall lung cancer (odds ratio OR = 1.7, 95% confidence interval CI = 0.92–3.14). No association was found between AA genotype and risk of lung cancer. In smokers, the combined AG+AA genotypes of CCND1 were found to be significant (OR = 1.9, 95% CI = 1.03–3.71, P = 0.03). No positive association was found between CCND1 genotypes in nonsmokers. The results suggest that the CCND1 A870G gene polymorphisms may increase the risk of lung cancer in smokers from north India.     

Age-related changes in the incidence of pineal gland calcification in Turkey: A prospective multicenter CT study

The goal of this cross-sectional observational study was to determine the incidence of pineal gland calcification (PGC), to investigate the interaction of PGC and aging, and to compare the incidence of PGC among the populations living in Turkey. In a prospective study the rate of PGC on CT scans of 1376 individuals in six referral centers from different regions of Turkey was investigated, with emphasis on effects of climatological parameters and aging on PGC. It was found that the incidence of PGC increased rapidly after first decade and the increase remains gradual thereafter, higher in males than in females for all age groups. There was a significant difference for incidence and degree of PGC between different clinics and between both sexes (p < 0.001). In addition, there was a significant difference for the degree of PGC between the clinics in low altitude group and those in high altitude group (p < 0.001 for each). Logistic regression analysis revealed that age, sex, altitude and intensity of sunlight exposure significantly affected the risk of PGC (odds ratios (OR) 1.335, 95% confidence intervals (CI) 1.261–1.414, p < 0.001; OR 1.900, 95% CI 1.486–2.428, p < 0.001; OR 0.715, 95% CI 0.517–0.990, p < 0.05; OR 0.997, 95% CI 0.994–0.999, p < 0.01, respectively). Furthermore, by multiple linear regression analysis, high altitude and increased intensity of sunlight exposure were found to affect the degree of PGC (β = 0.003, p < 0.001). It is concluded that there is a close relationship between PGC and the aforementioned parameters, supporting a link between the development of PGC and these. This study provides some reference data for new clinical studies on the putative role of pineal gland in future.     

Single nucleotide polymorphisms of the mannose-binding lectin are associated with susceptibility to primary biliary cirrhosis.

Although the immunopathogenesis of primary biliary cirrhosis (PBC) remains unknown, familial clustering of patients with PBC suggests an important role for genetic factors. In addition, recent data support the thesis that the mucosal immune response against intraluminal pathogens may be involved with the onset of PBC. Mannose-binding lectin (MBL) is a key factor in innate mucosal defenses and has several key single nucleotide polymorphisms (SNPs). To study whether MBL gene SNPs are associated with susceptibility to PBC, we studied 65 patients with PBC and 218 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence specific priming-polymerase chain reaction (SSP-PCR) to examine four polymorphic loci: two (H/L and X/Y) within the promoter region and the other two (P/Q and A/B) within exon-1. We also analyzed serum MBL concentrations. Interestingly, the prevalence of haplotype HYPA, leading to hyper-production of MBL, as well as HYPA/HYPA genotype were significantly increased in PBC compared to controls (0.53 vs. 0.44, P=0.031; 33.9%vs. 17.0%, P=0.003, respectively). Furthermore, individuals homozygous for HYPA had a significantly increased risk for PBC (odds ratio (OR)=2.51, 95% confidence interval (CI)=1.34-4.66). Our results demonstrate that the MBL genotype can be significantly associated with increased risk for PBC, and further, that increased production of MBL plays a critical role in immunopathogenesis.     

High-producing MBL2 genotypes increase the risk of acute and chronic carditis in patients with history of rheumatic fever

Rheumatic fever (RF) and its most severe sequela, chronic rheumatic heart disease (CRHD), are mediated by an abnormal immunological host response following a Streptococcus pyogenes oropharyngeal infection. Mannan-binding lectin (MBL), a collectin that activates complement, binds to N-acetylglucosamine, a molecule present on the streptococcus cell wall and on human heart valves. As high levels of MBL and MBL2 associated genotypes have previously been seen to be associated with CRHD, we investigated the association between MBL2 polymorphisms and the presence of acute carditis and arthritis in patients with a history of RF. Polymorphisms in exon 1 and in the X/Y promoter region of the MBL2 gene were determined by PCR-SSP in 149 patients with a history of RF and 147 controls. Genotypes associated with the high production of MBL (YA/YA and YA/XA) were more frequent in the patients with acute (26/35, 74%) and chronic carditis (79/107, 74%) when compared to the controls (79/147, 54%; OR 2.48, 95% CI 1.09-5.67, p=0.035 and OR 2.42, 95% CI 1.41-4.16, p=0.001, respectively). Logistic regression analysis showed that MBL levels >2800ng/ml increased the risk of CRHD (OR 2.91, 95% CI 1.41-6.03, p=0.003). Among the RF patients without cardiac sequela, YA/YA and YA/XA genotypes were significantly associated with acute carditis when compared to the patients without this clinical manifestation (26/28, 93% vs. 9/14, 64%, OR 7.22, 95% CI 1.18-43.98, p=0.031); on the other hand, arthritis was more frequently observed in those patients presenting MBL2 genotypes related to the low production of MBL (10/14, 71% vs. 10/28, 36%; p=0.048, OR 0.22, 95% CI 0.05-0.89). We concluded that MBL2 genotypes associated with the high production of MBL seem to be involved in the pathogenesis of rheumatic carditis and its progression to CRHD.     

Association study of LMP gene polymorphisms in Mexican patients with spondyloarthritis

To evaluate the role of LMP (low molecular weight protein) genes as susceptibility markers for spondyloarthritis (SpA), LMP gene polymorphisms were analyzed in 223 Mexican patients with SpA (81 undifferentiated SpA [U-SpA], 117 with ankylosing spondylitis [AS], 25 with reactive arthritis) and in 139 ethnically matched healthy individuals. LMP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The LMP2 and LMP7 allele frequencies were similar in patients and healthy controls. Genotype analysis revealed an increased frequency of LMP2 R/R genotype in the whole group of SpA (pC = 0.003, OR = 2.06, 95%CI = 1.3–3.25) and in the clinical subgroups of AS (pC = 0.039, OR = 1.88, 95%CI = 1.1–3.22) and U-SpA (pC = 0.003, OR = 2.56, 95%CI = 1.37–4.8) compared with healthy controls. Analysis in the LMP7 did not reveal significant differences in patients and healthy controls. The HLA-B27-negative AS subgroup also showed an increased frequency of LMP2 R/R genotype (pC = 0.027, OR = 4.81, 95%CI = 1.21–22.13). The LMP2-R/R AS patients were younger than LMP2-H/R and H/H patients at onset of the disease (16.0 ± 6.8 years for R/R, 22.0 ± 11.2 years for H/R and 28.6 ± 10.9 years for H/H) (p < 0.05). The data suggest that, besides HLA-B27, LMP2 genotypes are also involved in the genetic susceptibility to develop AS in Mexicans. Furthermore, the age at onset of this disease might also be influenced by genotypes of this gene.     

MCP-1, RANTES, and SDF-1 polymorphisms in Mexican patients with systemic lupus erythematosus

Chemokines and cytokines play an important role in the inflammatory development and progression of autoimmune diseases. The aim of the present study was to evaluate the role of MCP-1, SDF-1, and RANTES polymorphisms as susceptibility markers for systemic lupus erythematosus (SLE) in a group of Mexican patients. MCP-1-2518, SDF-1 G801A, and RANTES-28 polymorphisms were determined in 242 patients with SLE and 220 ethnically matched healthy controls by the polymerase chain reaction–restriction fragment length polymorphism technique. The differences between patients and healthy controls were evaluated by χ², Fisher’s exact test, and Woolf method for odds ratio. A moderately increased frequency of MCP-1-2518 A allele (p = 0.033, pC = NS) and AA genotype (p = 0.017, pC = NS) existed in SLE patients compared with healthy controls. There was a relationship between polymorphisms and some clinical and laboratory characteristics. SLE patients with and without antiphospholipid syndrome demonstrated different distribution of SDF-1 G801A genotype frequencies. On the other hand, patients with leukopenia, anti-dsDNA, and antiphospholipid autoantibodies demonstrated different MCP-1-2518 genotype distribution compared with patients without these features. Our results suggest that MCP-1 polymorphism is moderately associated with the genetic susceptibility to SLE in Mexican individuals. The polymorphisms could be related to specific clinical and laboratory characteristics in these patients.     

Anti-endothelial cell antibodies in rheumatic heart disease

To evaluate the anti‐endothelial cell antibodies (AECA), anti‐cardiolipin antibodies (aCL) and serum mannose‐binding lectin (MBL) profiles of a large cohort of Yemeni patients with rheumatic heart disease (RHD) and to correlate these findings with clinical features of the disease. Patients (n = 140) were recruited from Al‐Thawra Hospital in Sana'a, Yemen. All had RHD diagnosed according to modified Jones' criteria. We also studied 140 sex‐ and age‐matched healthy blood donors from the same area. Echocardiography was performed according to the recommendations of the American Society of Echocardiography. Solid phase enzyme‐linked immunosorbent assays (ELISAs) were used to measure AECA and aCL titres and serum MBL levels. Forty per cent of the patients were AECA‐positive, but only 7·8% were positive for aCL antibodies. Serum MBL levels were significantly lower in the RHD group (median 4221 ng/ml versus 5166 ng/ml in healthy controls). AECA titres were correlated positively with patient age, duration of RHD and the severity of aortic stenosis, as determined by echocardiographic findings. In several autoimmune rheumatic diseases, such as systemic lupus erythematosus, vasculitis and scleroderma, AECA have been shown to play pathogenic roles by producing proinflammatory and procoagulant effects (increased expression of adhesion molecules and tissue factors, increased cytokine release) in endothelial cells. In RHD, these autoantibodies might represent a pathological link between activation of the valvular endothelium and valvular damage.     

Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with B-cell chronic lymphocytic leukemia in the Polish population

Abnormal expression of the costimulatory molecules cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28, and inducible co-stimulator (ICOS) leads to disturbances of immune response and an increased risk of cancer. An extended study was undertaken to evaluate the association among the polymorphisms CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CD28c.17+3T>C, and ICOSc.1554+4GT(8_15) and susceptibility to B-cell chronic lymphocytic leukemia (B-CLL) in the Polish population. The study revealed increased frequency of the CTLA-4g.319C>T [T] allele and the CTLA-4g.319C>T [T] phenotype in B-CLL patients compared with healthy controls (p = 0.003, odds ratio [OR] = 1.73; and p = 0.009, OR = 1.74, respectively). The presence of the CD28c.17+3T>C [C] allele and the CD28c.17+3T>C [C] phenotype increased the OR of B-CLL to 1.59 (p = 0.007) and 1.74 (p = 0.007), respectively. Either CTLA-4g.319C>T or CD28c.17+3T>C was associated with time to Rai stage progression. The distributions of the alleles and genotypes of the ICOS gene significantly differed between patients and controls (p = 0.0009 and p = 0.006, respectively). Individuals possessing short alleles were 2.02 times more prone to B-CLL than others (p = 0.001), whereas carriers of long alleles were protected from B-CLL (p = 0.02, OR = 0.62). The haplotype association study and multivariate analysis confirmed the association of CTLA-4g.319C>T and ICOSc.1554+4GT(8_15) gene polymorphisms with B-CLL. The polymorphic sites CTLA-4c.49A>G and CTLA-4g.*642AT(8_33) did not correlate with B-CLL. Our results are the first in the literature to report that gene polymorphism of the costimulatory molecules CTLA-4, CD28, and ICOS contributes to susceptibility to B-CLL.     

Catechol-O-methyltransferase gene polymorphism is associated with risk of psychosis in Alzheimer Disease

There is emerging evidence that psychosis in Alzheimer Disease (AD) represents a clinically relevant phenotype with a distinct biological process. It has been reported that a functional polymorphism of the catechol-O-methyltransferase (COMT) gene predisposes to an increased risk for schizophrenia and likely to psychosis susceptibility.

Aim of this study was to evaluate functional COMT genetic variation as a risk factor for psychosis in Alzheimer Disease.

One hundred eighty-one AD patients and 208 age-matched controls underwent clinical and neuropsychological examination, behavioural and psychiatric disturbances evaluation, and ApoE and COMT genotyping.

The distribution of COMT genotypes did not significantly differ in AD compared to controls. Among patients with psychosis (32.6%), 88.1% were COMT*H carriers (COMT H/H or COMT H/L, p < .01). The Odds Ratio (OR) for risk of psychosis in COMT*H carriers was 2.66 (confidence interval, CI 95%: 1.6–6.62), taking into account possible confounding factors. A comparable influence of COMT polymorphism on psychosis over the course of the disease was reported. These findings suggest that COMT polymorphism influences on the risk of psychosis since the early stages, and claims for the possibility to identify distinct phenotypes on genetic basis among AD patients.     

Cytotoxic T lymphocyte-associated antigen-4 polymorphism in patients with rheumatic heart disease

Acute rheumatic fever (ARF) is a systemic inflammatory disease occurring as a consequence of an exaggerated immune response to group A, beta haemolytic streptococcal pharyngitis. The molecular mimicry between human target organs/tissues and specific components of the infectious organism leads to the development of autoimmune reactions and cardiac tissue damage in rheumatic heart disease (RHD). Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation and proliferation during the immune response. CTLA-4 gene polymorphism has been shown to affect the inhibitory function of CTLA-4. We aimed to analyze the association of CTLA-4 gene locus at position 49 of exon 1 with susceptibility to ARF/RHD. This study included a total of 98 patients with RHD as a sequela of ARF, who fulfilled the revised classification criteria of Jones and 154 healthy unrelated controls. CTLA-4 +49 A/G polymorphism was genotyped by using PCR-RLFP technique. Data was analyzed by binary logistic regression models. The frequencies of GG, GA and AA genotypes were found to be 14%, 47% and 39%, respectively, in patients and 6%, 45% and 49%, respectively, in controls. The GG genotype was found to be significantly different between patients and controls (OR: 3.11; P = 0.016). GA and AA genotypes did not statistically differ between patients and controls. Our data showed a significant association of +49G /G polymorphism in a small patient group with RHD.     

Menstrual and reproductive factors and hip fractures in post menopausal women

Objectives: We analyzed the relationship between menstrual and reproductive history and risk of hip fractures in post-menopausal women using data from an Italian case-control study. Methods: Cases were 206 post-menopausal women admitted for fractures of the hip/proximal femur to a network of teaching and general hospitals in Milan, Italy. The comparison group consisted of 590 post-menopausal women admitted to the same network of hospitals for acute, non-neoplastic, non-hormone-related conditions, other than traumatic or orthopedic disorders. Odds ratios (OR) of hip fracture were derived from unconditional multiple logistic regression. Results: No relation emerged between risk of hip fractures and age at menarche, lifelong menstrual cycle pattern and age at menopause. In comparison with women with age at menopause ≥53 years, the multivariate OR of hip fractures were 1.2, 1.1, 1.2 and 0.5 in women with menopause at 50–52, 45–49, 40–44 and before 40 years (X₁² trend 0.21). In comparison with nulliparae, the estimated age-adjusted OR was 0.6 (95% confidence interval, CI, 0.4–0.9) for parous women, but the multivariate estimate was not significant (OR 0.8, 95% CI 0.6–1.3) and the multivariate trend in risk with number of births was not significant either. No relation emerged between hip fractures and age at first and last birth, and history of abortions. Conclusions: This study found no relevant influence of menstrual and reproductive factors on the risk of hip fractures in post-menopausal women. However, this is not in contrast with the observation of a short-term effect of menopause and, more in general, female hormone levels on osteoporosis and hence on hip fractures.     

Paroxysmal nocturnal hemoglobinuria: significant association with specific HLA-A, -B, -C, and -DR alleles in an Italian population

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the expansion of a PIG-A mutated hematopoietic stem cell. An immune-mediated origin has been suggested for this disease. Because HLA genes represent a susceptibility factor for autoimmunity, we investigated HLA genotype in 42 Italian PNH patients compared with 301 control subjects of the same ethnic origin. A significantly increased frequency of the HLA class I alleles A*0201 (p < 0.05), B*1402 (p < 0.001), and Cw*0802 (p < 0.005), and of the HLA class II DRB1*1501 (p < 0.01) with the linked DQB1*0602 (p ≤ 0.05) and DRB1*01 (p ≤ 0.05) with the linked DQB1*0501 (p ≤ 0.01) alleles, has been observed. Notably, a fourfold increase of the haplotype B*1402, Cw*0802 (p < 0.0005) and a 15-fold increase of the Mediterranean haplotype A*33, B*1402, Cw*0802, DRB1*0102, DQB1*0501 (p < 0.005) was also revealed. This association may provide new insights into the autoimmune pathogenesis of PNH.     

The APOC3 SstI polymorphism is weakly associated with sporadic Alzheimer's disease in a Chinese population

In order to clarify the relationship of apolipoprotein CIII (APOC3) polymorphism and sporadic Alzheimer's disease (AD) in Chinese, 165 sporadic AD patients and 174 age-matched elderly individuals were genotyped for the APOC3 SstI and apolipoprotein E (APOE) HhaI polymorphisms. As the result, the APOC3 3017G allele was found to be associated with AD in APOE 4 allele noncarriers (χ² = 4.433, P = 0.035), and the risk estimate of allele C versus G resulted in an OR of 1.56 (95% CI: 1.03–2.37), although in total no significant differences of allelic or genotypic frequencies between patients and controls were found. Assessment of interaction between APOE 4 and APOC3 3017G status presented an adjusted odds ratio of 0.62 (95% CI: 0.37–1.03) with a borderline significant P-value (P = 0.066). Therefore, we conclude that the rare APOC3 G allele may offer some protection against the development of sporadic AD in APOE 4 noncarriers in Chinese.     

中国白族人群MBL基因SNP及其单倍型与基因型的研究

目的：研究中国云南白族人甘露聚糖结合凝集素（MBL）基因单核苷酸多态性（SNP）及其单倍型与基因型。方法：对MBL基因启动子区SNP位点-550G／C（称H／L等位基因）、-221C／G（X／Y）、＋4C／T（P／Q）已明确的白族DNA样本，采用序列特异性引物．多聚酶链反应技术检测结构基因第一外显子点突变CGT52TGT、CCC54GAC和CCA57CAA（分别称为D、B、C等位基因，野生型即A），并分析MBL基因的单倍型与基因型。结果：只检出GGC54GAC点突变，其频率为0．100；检出的5种单倍型及其频率是：HYPA0．250、LXPA0．107、LYQA0．407、LYPA0．135、LYPB0．100；各基因型及其频率为：LYPA／LYPA0．043、LXPA／LYQA0．143、LYPA／LYPB0．014、HYPA／LYQA0．086、LYPA／LYQA0．157、HYPA／LYPA0．014、LYPB／LYQA0．143、HYPA／LYPB0．043、LXPA／LXPA0．014、HYPA／LXPA0．043、LYQA／LYQA0．143、HYPA／HYPA0．157。结论：中国白族人群MBL基因存在GGC54GAC点突变，单倍型以LYQA和HYPA为主，基因型则多见LYPA／LYQA、HYPA／HYPA、LX—PA／LYQA、LYPB／LYQA和LYQA／LYQA。     

Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women - results of the Danish Osteoporosis Prevention Study

Objectives: To study the fracture reducing potential of hormonal replacement therapy (HRT) in recent postmenopausal women in a primary preventive scenario. Methods: Prospective controlled comprehensive cohort trial: 2016 healthy women aged 45–58 years, from three to 24 months past last menstrual bleeding were recruited from a random sample of the background population. Mean age was 50.8±2.8 years, and the number of person years followed was 9335.3. There were two main study arms: a randomised arm (randomised to HRT; n=502, or not; n=504) and a non-randomised arm (on HRT; n=221, or not; n=789 by own choice). First line HRT was oral sequential oestradiol/norethisterone in women with intact uterus and oral continuous oestradiol in hysterectomised women. Results: After five years, a total of 156 fractures were sustained by 140 women. There were 51 forearm fractures in 51 women. By intention-to-treat analysis (n=2016), overall fracture risk was borderline statistically significantly reduced (RR=0.73, 95% CI: 0.50–1.05), and forearm fracture risk was significantly reduced (RR=0.45, 95% CI: 0.22–0.90) with HRT. Restricting the analysis to women who had adhered to their initial allocation of either HRT (n=395) or no HRT (n=977) showed a significant reduction in both the overall fracture risk (RR=0.61, 95% CI: 0.39–0.97) and the risk of forearm fractures (RR=0.24, 95% CI: 0.09–0.69). Compliance with HRT was 65% after five years. Conclusions: It is possible to reduce the number of forearm fractures and possibly the total number of fractures in recent postmenopausal women by use of HRT as primary prevention.