No association between DCP1 genotype and late‐onset Alzheimer disease

In a study of 261 patients with Alzheimer disease (AD) and 306 cognitively normal control subjects from Germany, Switzerland, and Italy, we found no association between genotype counts or allelic frequencies of DCP1, the gene encoding angiotensin‐converting enzyme. In accordance with several other studies, our data could not confirm previous association findings. Critical review about all studies available on DCP1 genotyping and AD, age‐associated cognitive decline, longevity, and other conditions revealed remarkable inconsistencies. Several studies showed significant deviations of genotype counts from Hardy Weinberg equilibrium (HWE). Deviations from HWE may limit the comparability of study results and require clarification before drawing conclusions with respect to disease risk, health conditions, or longevity in association with DCP1 genotype. © 2002 Wiley‐Liss, Inc.     

The associations between CYP24A1 polymorphisms and cancer susceptibility: A meta-analysis and trial sequential analysis

Purpose

Published data have shown that vitamin D may have a protective effect on cancer development. CYP24A1, the main enzyme responsible for the degradation of active vitamin D, plays an important role in many cancer related cellular processes. Up to now, relationships between CYP24A1 polymorphisms and cancer susceptibility have been widely investigated, whereas the results are inconsistent. The aim of present meta-analysis was to explore the associations between CYP24A1 polymorphisms and cancer susceptibility.

4-Locus high-resolution HLA allele and haplotype frequencies in Costa Ricans from African-Caribbean descent

A total of 102 Costa Ricans of African-Caribbean descent were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, and -DRB1 using sequence-based typing methods. The respective allele and extended haplotype frequencies, as well as Hardy-Weinberg proportions were calculated. The most frequent extended haplotype identified was A*01:01:01-B*08:01:01-C*07:01:01-DRB1*03:01:01G, with an estimated frequency of 1.96%. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name “Costa Rica African-Caribbeans” and the identifier AFN3607.     

Association between NME1 polymorphisms and cancer susceptibility: A meta-analysis based on 1644 cases and 2038 controls

The association between polymorphisms in the nucleoside diphosphate kinase 1 (NME1) gene and overall risk of cancer remains to be elucidated. Here, we performed a meta-analysis of the association between rs16949649, rs2302254, and rs34214448 polymorphisms in the NME1 gene and cancer risk. PubMed, Web of Science, and CNKI databases (as of June 6, 2017) were searched. Eight studies, encompassing 1644 cases and 2038 controls, were selected. The results revealed no significant relationship between NME1 polymorphisms and overall cancer susceptibility. Interestingly, the rs16949649 polymorphism was associated with increased susceptibility to gynecological cancer (heterozygous model: odds ratio [OR]?=?1.74, 95% confidence interval [CI]?=?1.06–2.86, P?=?0.029). The rs2302254 polymorphism was linked to decreased susceptibility to gastric cancer in the other groups (recessive model: OR?=?0.53, 95% CI?=?0.28–0.98, P?=?0.045). The rs34214448 polymorphism correlated significantly with increased susceptibility to non-small cell lung cancer according to all genetic models (P?<?0.05) and was linked to decreased risk in cervical cancer (recessive model: OR?=?0.51, 95% CI?=?0.27–0.94, P?=?0.031). Thus, our meta-analysis found rs16949649 associated with increased susceptibility to gynecological cancer and rs2302254 was linked to reduced gastric cancer risk; additional, larger studies are required to confirm these findings.     

The association of the JAK2 46/1 haplotype with non-splanchnic venous thrombosis

Background

The inherited JAK2 46/1 haplotype is strongly associated with the development of myeloproliferative neoplasms (MPNs), and its increased frequency has also been reported in splanchnic venous thrombosis (SVT). In the present study, the role of the JAK2 46/1 haplotype in non-splanchnic venous thrombosis (non-SVT) was investigated.

Methods and Results

We genotyped 438 patients with non-SVT, 226 patients with MPNs and 459 healthy controls for three single nucleotide polymorphisms (SNPs) which tag the JAK2 46/1 haplotype (rs12342421 G > C, rs12343867 T > C and rs10974944 C > G). We found statistically significant association of the rs12342421 GC + CC genotypes (OR = 1.40; p = 0.023) and the rs12343867 TC + CC genotypes (OR = 1.83; p = 7.02x10^- 5) with non-SVT. We also found that the CC haplotype of these two SNPs was associated with an increased risk of the disease (OR = 1.68; p = 0.009). Stratification analysis indicated that the observed association of the JAK2 46/1 haplotype with non-SVT was probably largely free of confounding effect of thrombophilic risk factors. In addition, we established a strong association of SNPs rs12342421 and rs10974944 and their CG haplotype with MPNs and with JAK2 V617F-positive MPNs.

Conclusions

This study provides statistical evidence that SNPs rs12342421 and rs12343867 are associated with an increased risk of non-SVT. Consistently, haplotypes of the SNPs were also associated with non-SVT risk, suggesting that inherited genetic variation in the JAK2 gene may play a role in the pathogenesis of non-SVT. Furthermore, the reported associations of the JAK2 46/1 haplotype with MPNs as well as with the occurrence of the JAK2 V617F mutation in MPNs were confirmed.     

High-resolution HLA haplotype frequencies of stem cell donors in Germany with foreign parentage: How can they be used to improve unrelated donor searches?

In hematopoietic stem cell transplantation, human leukocyte antigens (HLA), usually HLA loci A, B, C, DRB1 and DQB1, are required to check histocompatibility between a potential donor and the recipient suffering from a malignant or non-malignant blood disease. As databases of potential unrelated donors are very heterogeneous with respect to typing resolution and number of typed loci, donor registries make use of haplotype frequency-based algorithms to provide matching probabilities for each potentially matching recipient/donor pair. However, it is well known that HLA allele and haplotype frequencies differ significantly between populations. We estimated high-resolution HLA-A, -B, -C, -DRB1 haplotype and allele frequencies of donors within DKMS German Bone Marrow Donor Center with parentage from 17 different countries: Turkey, Poland, Italy, Russian Federation, Croatia, Greece, Austria, Kazakhstan, France, The Netherlands, Republic of China, Romania, Portugal, USA, Spain, United Kingdom and Bosnia and Herzegovina. 5-locus haplotypes including HLA-DQB1 are presented for Turkey, Poland, Italy and Russian Federation. We calculated linkage disequilibria for each sample. Genetic distances between included countries could be shown to reflect geography. We further demonstrate how genetic differences between populations are reflected in matching probabilities of recipient/donor pairs and how they influence the search for unrelated donors as well as strategic donor center typings.     

Genetic study confirms association of HLA-DPA101:03 subtype with ankylosing spondylitis in HLA-B27-positive populations

The association of human leukocyte antigen (HLA)-B27 with ankylosing spondylitis (AS) has been known for over 38 years. However, it is not the only gene associated with AS. The aim of this study was to confirm the association of HLA markers around HLA-DPA1/DPB1 region with AS in HLA-B27 positive populations. Five SNPs (rs422544, rs6914849, rs92777535, rs3128968 and rs2295119) from the HLA-DPA1/DPB1 region were genotyped in 340 individuals HLA-B27-positive from Portugal (137 AS patients and 203 healthy controls). Characterizations of HLA-DPA1/DPB1 alleles were also performed. rs422544 revealed a significant association with AS (P < 0.05) and sliding windows (SW) analysis showed association of some groups of adjacent SNPs within HLA-DPA1/DPB1 region with AS (P < 0.05). We also found association of the HLA-DPA1^∗01:03 allele with AS (P < 0.05). This is the first study that confirms the association of HLA markers and haplotypes around HLA-DPA1 and HLA-DPB1 with AS.     

A functional polymorphism in estrogen receptor alpha gene is associated with Japanese methamphetamine induced psychosis

Background

A recent study reported an association between rs2234693, which influences enhancer activity levels in estrogen receptor alpha gene (ESR1), and schizophrenia. This study reported that schizophrenic patients with the CC genotype have significantly lower ESR1 mRNA levels in the prefrontal cortex than patients with other genotypes. The symptoms of methamphetamine induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an association analysis of rs2234693 with Japanese methamphetamine induced psychosis patients.

Method

Using rs2234693, we conducted a genetic association analysis of case-control samples (197 methamphetamine induced psychosis patients and 197 healthy controls). The age and sex of the control subjects did not differ from those of the methamphetamine induced psychosis patients.

Results

We detected a significant association between ESR1 and methamphetamine induced psychosis patients in allele/genotype-wise analysis. For further interpretation of these associations, we performed single marker analysis of subjects divided by sex. Rs2234693 was associated with male methamphetamine induced psychosis.

Discussion

Our results suggest that rs2234693 in ESR1 may play a role in the pathophysiology of Japanese methamphetamine induced psychosis patients.