Association Between VDR FokI Polymorphism and Intervertebral Disk Degeneration

Intervertebral disk degeneration(IDD) is strongly associated with genetic predisposition and environmental susceptibility. Several studies been conducted to investigate the potential association between IDD and Fok I polymorphism located in the gene encoding the vitamin D receptor(VDR), and inconsistent conclusions had been reached among different ethnic populations. In order to assess the association between the Fok I polymorphism and the risk of IDD, we performed a comprehensive and systematic meta-analysis. Candidate articles were retrieved from Pub Med,EMBASE, China National Knowledge Infrastructure(CNKI), and China Biology Medical(CBM) with strict inclusion criteria in January 2015. Among the 54 articles that were retrieved, only eight studies met the inclusion criteria. The pooled data analysis based on allele contrast, homozygote, heterozygote, dominant, and recessive models revealed no significant correlation between the Fok I polymorphism and the risk of IDD. However, when stratified by ethnicity, significant associations were detected for Hispanics based on allele contrast(OR = 1.395, 95% CI = 1.059–1.836,P = 0.018), homozygote(OR = 1.849, 95% CI = 1.001–3.416, P = 0.049), heterozygote(OR = 1.254, 95% CI = 1.049–1.498, P = 0.013), and dominant(OR = 1.742, 95%CI = 1.174–2.583, P = 0.006) models, and for Asians using the dominant model(OR = 1.293,95% CI = 1.025–1.632, P = 0.030), whereas there is no significant association detected for Caucasians. In conclusion, Fok I polymorphism is not generally associated with IDD, but there is increased risk for IDD in Hispanics and Asians carrying Fok I allele T.     

Association Between rs1344706 of ZNF804A and Schizophrenia:A Meta-analysis

Schizophrenia is one of the most serious mental diseases found in humans. Previous studies indicated that the single nucleotide polymorphism（SNP） rs1344706 in the gene ZNF804 A encoding zinc finger protein 804 A was associated with schizophrenia in Caucasian population but not in Chinese Han population. However, current results are conflicting in Asian population. In the present study, a meta-analysis was performed to revisit the association between rs1344706 and the risk of schizophrenia in Asian, Caucasian and other populations. Electronic search of Pub Med database identified 25 case–control studies with available genotype frequencies of rs1344706 for the meta-analysis,involving a total of 15,788 cases and 22,654 controls. A pooled odds ratio（OR） with 95% confidence interval（CI） was used to assess the association. The current meta-analysis showed an association between rs1344706 and schizophrenia in Caucasian populations（P = 0.028, OR = 1.138, 95% CI：1.014–1.278; P = 0.004 for heterogeneity） and Asian populations（P = 0.008, OR = 1.092, 95%CI： 1.023–1.165; P = 0.001 for heterogeneity）, but not in other populations（P = 0.286,OR = 1.209, 95% CI： 0.853–1.714, P = 0.120 for heterogeneity）. Egger’s test（P 〉 0.05） and Begg’s test（P 〉 0.05） are both suggestive of the lack of publication bias for the included studies. Thus, the absence of association in other populations suggests a genetic heterogeneity in the susceptibility of schizophrenia and demonstrates the difficulties in replicating genome-wide association study findings regarding schizophrenia across different ethnic populations. To validate the association between rs1344706 and schizophrenia, further studies with larger participant populations worldwide are needed.     

Variant rs2237892 of KCNQ1 Is Potentially Associated with Hypertension and Macrovascular Complications in Type 2 Diabetes Mellitus in A Chinese Han Population

KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus(T2DM) in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KCNQ1 and T2 DM complications remain unclear. To further analyze the association between different alleles at the single nucleotide polymorphism(SNP) rs2237892 within KCNQ1 and TD2 M and its complications, we conducted a case-control study in a Chinese Han population. The C allele of rs2237892 variant contributed to susceptibility to T2DM(odds ratio [OR], 1.45; 95% confidence interval [CI], 1.20–1.75). Genotypes CT(OR, 1.97; 95% CI,1.24–3.15) and CC(OR, 2.49; 95% CI, 1.57–3.95) were associated with an increased risk of T2 DM. Multivariate regression analysis was performed with adjustment of age, gender, and body mass index. We found that systolic blood pressure(P = 0.015), prevalence of hypertension(P = 0.037), and risk of macrovascular disease(OR, 2.10; CI, 1.00–4.45) were significantly higher in subjects with the CC genotype than in the combined population with genotype either CT or     

SARS-CoV Genome Polymorphism： A Bioinformatics Study

A dataset of 103 SARS-CoV isolates （101 human patients and 2 palm civets） was investigated on different aspects of genome polymorphism and isolate classification. The number and the distribution of single nucleotide variations （SNVs） and insertions and deletions, with respect to a “profile”, were determined and discussed （“profile” being a sequence containing the most represented letter per position）. Distribution of substitution categories per codon positions, as well as synonymous and non-synonymous substitutions in coding regions of annotated isolates, was determined, along with amino acid （a.a.） property changes. Similar analysis was performed for the spike （S） protein in all the isolates （55 of them being predicted for the first time）. The ratio Ka/Ks confirmed that the S gene was subjected to the Darwinian selection during virus transmission from animals to humans. Isolates from the dataset were classified according to genome polymorphism and genotypes. Genome polymorphism yields to two groups, one with a small number of SNVs and another with a large number of SNVs, with up to four subgroups with respect to insertions and deletions. We identified three basic nine-locus genotypes： TTTT/TTCGG, CGCC/TTCAT, and TGCC/TTCGT, with four subgenotypes. Both classifications proposed are in accordance with the new insights into possible epidemiological spread, both in space and time.     

Preliminary computational modeling of nitric oxide synthase 3 interactions with caveolin-1： influence of exon 7 Glu298Asp polymorphism

The significance of endothelial nitric oxide synthase 3 （NOS3） activity has been recognized for many years, however it was only recently that the complicated regulation of this constitutively expressed enzyme in endothelial cells was identified. A critical component of the NOS3 regulatory cyde in endothelial cells is its intracellnlar localization to caveolae. The caveolar coordination of NOS3, more specifically its interaction with caveolin-1 （Cav-1）, plays a major role in normal endothelial NOS3 activity and vascular bioavailability of nitric oxide. We have recently shown that the presence of NOS3 exon 7 Glu298Asp polymorphism caused diminished shear-dependent NOS activation, was less extensively associated with caveolae, and had a decreased degree of interaction with Cav-1. Here, we carried out preliminary investigations to identify possible mechanisms of the genotype-dependent endothelial cell responses we observed in our previous investigations. Through this approach we tested the hypothesis that computer simulations could provide insights regarding the contribution of this single nucleotide polymorphism to regulation of the NOS3 isoform. We observed that in the Glu/Asp and Asp/Asp mutant genotypes, the amount of NOS3 associated with Cav-1 was significantly lower. Additionally, we have shown, using a theoretical computational model, that mutation of an amino acid at position 298 might affect the protein-protein interactions and localization of the NOS3 protein. These alterations might also affect the protein function and explain the enhanced disease risk associated with the presence of Glu298Asp polymorphism in the NOS3 protein.     

Association study of the single nucleotide polymorphisms in adiponectin-associated genes with type 2 diabetes in Han Chinese

Single-nucleotide polymorphisms （SNPs） of ADIPOQ, ADIPOR1, and ADIPOR2 have been associated with type 2 diabetes mellitus （T2DM）, but there are many conflicting results especially in Chinese populations. To investigate the contribution of the adiponectin genes and their receptors to T2DM, a case-control study was performed and 11 SNPs ofADIPOQ, ADIPOR1, and ADIPOR2 were genotyped in 985 T2DM and 1,050 control subjects, rs 16861194 （-11426 A〉G） in the putative promoter of ADIPOQ was associated with T2DM （P = 0.007; OR = 1.29, 95% CI 1.08-1.55）. None of the other 10 SNPs were associated with T2DM in this study, although rs2241766 and rs1501299 were reported to be associated with T2DM in previous Chinese studies. There was also no significant difference found from the ADIPOQ haplotype analysis, which contains rs 16861194. In addition, we also assessed potential gene-gene interactions in three genes and no interactions were found. In conclusion, our results supported the ADIPOQ gene as a possible risk factor for type 2 diabetes in Han Chinese population.     

New Gene Variants Associated with the Risk of Chronic HBV Infection

Some patients with chronic hepatitis B virus(HBV) infection failed to clear HBV, even persistently continue to produce antibodies to HBV. Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV. The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive) compared with 102 control patients(antiHBs positive, HBsAg negative). Over 80% of individual sequences displayed 209 sequence coverage. Adapters,uncertain bases [10% or low-quality base calls([50%) were filtered and compared to the human reference genome hg19. In the second stage, 579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage. Although there were no significant associated gene variants in the first stage, two significant gene associations were discovered when the two stages were assessed in a combined analysis. One association showed rs506121-‘‘T' allele [within the dedicator of cytokinesis 8(DOCK8) gene] was higher in chronic HBV infection group than that in clearance group(P = 0.002, OR = 0.77, 95% CI [0.65, 0.91]). The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9) gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P = 0.0003, OR = 1.35, 95% CI [1.15, 1.58]). Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection.     

南京汉族群体肺癌易感性相关基因的研究

为了探讨南京汉族群体肺癌易感性相关基因,我们采用1:1病例对照研究方法,以PCR—RFLP技术检测了152对肺癌和健康对照的CYP1A1、CYP2E1、GSTM1、GSTT1、GSTP1、mEH和NQO1基因的基因型并分析其与肺癌的相关性。结果发现携带CYP1A1突变基因型（wt/mt和mt/mt）的个体明显增加患肺鳞癌的风险(OR=2.31,95%CI=1.23-4.36);GSTT1（-）基因型可使肺癌发生的风险增加2.06倍（95%CI=1.30-3.24）;具有NQO1wt/mt与mt/mt基因型者发生肺癌的风险也有所增高（OR=1.66,95CI%=1.01-2.74）; CYP1A1突变基因型与GSTT1缺失基因型、CYP1A1突变基因型与NQO1突变基因型对肺癌的发生存在协同作用,同时具有两种易感基因型的个体更容易发生肺癌。研究结果表明,CYP1A1、GSTT1、NQO1基因可能与南京汉族群体肺癌遗传易感性有关,基因型之间的联合检测更有助于高危人群的筛选。Abstract: To investigate the genes related to lung cancer susceptibility in Nanjing Han population, China, a 1:1 matched case-control study was performed in which 152 hospital controls were matched to the 152 original lung cancer cases. The polymorphisms of CYP1A1, CYP2E1, GSTM1, GSTT1, GSTP1, mEH and NQO1 genes were analyzed by PCR—RFLP assay. The results showed that the heterozygote and mutation homozygote genotypes of CYP1A1 were related to the risk of squamous cell carcinoma (OR=2.31, 95%CI=1.23-4.36). The risk of suffering from lung cancer was increased 2.06-fold in the individuals with GSTT1（-） genotype (95%CI= 1.30-3.24). The genotype of NQO1 wt/mt and mt/mt was found also to be associated with the risk of lung cancer (OR=1.66,95%CI=1.01-2.74). It was shown that there was no difference in the genotype distribution of CYP2E1, GSTM1, GSTP1 or mEH between cases and controls. Furthermore, stratified analysis suggested that the combination of genotypes of both CYP1A1 and GSTT1 enzymes had a synergistic action in risk of lung cancer (OR=3.41, 95%CI =1.77-6.55). Similarly, there was a cooperation between CYP1A1 mutation genotype and NQO1 mutation genotype (OR=2.45, 95%CI=1.13-5.31). This study suggested that CYP1A1, GSTT1 and gene NQO1 polymorphisms might be associated with the susceptibility to lung cancer in Nanjing Han population. Analysis of gene-gene interactions was helpful to identification of susceptible individuals and screening high-risk population to lung cancer.     

Association between endothelial nitric oxide synthase(ENOS) G894T polymorphism and high altitude(HA) adaptation: a meta-analysis

Objective: Highland natives adapt well to the hypoxic environment at high altitude(HA). Several genes have been reported to be linked to HA adaptation. Previous studies showed that the endothelial nitric oxide synthase(ENOS) G894 T polymorphism contributed to the physiology and pathophysiology of humans at HA by regulating the production of NO. In this meta-analysis, we evaluate the association between the ENOS G894 T polymorphism and HA adaptation through analyzing the published data. Methods: We searched all relevant literature about the ENOS G894 T polymorphism and HA adaptation in Pub Med, Medline, and Embase before Step 2015. A random-effects model was applied(Revman 5.0), and study quality was assessed in duplicate. Six studies with 634 HA native cases and 621 low-altitude controls were included in this meta-analysis. Results: From the results, we observed that the wild-type allele G was significantly overrepresented in the HA groups(OR=1.85; 95% CI, 1.47–2.33; P0.0001). In addition, the GG genotype was significantly associated with HA adaptation(OR=1.99; 95% CI, 1.54–2.57; P0.0001). Conclusion: Our results showed that in 894 G allele carriers, the GG genotype might be a beneficial factor for HA adaptation through enhancing the level of NO. However, more studies were needed to confirm our findings due to the limited sample size.     

Genetic Mapping of Laminaria japonica and L. Iongissima Using Amplified Fragment Length Polymorphism Markers in a ＂Two-Way Pseudo- Testcross＂ Strategy

With a ＂two-way pseudo-testcross＂ mapping strategy, we applied the amplified fragment length polymorphism （AFLP） markers to construct two moderate density genetic linkage maps for Laminaria. The linkage maps were generated from the 60 progenies of the F1 cross family （Laminaria iongissima Aresch. × L. Japonica Miyabe） with twenty pairs of primer combinations. Of the 333 polymorphic loci scored in 60 progenies, 173 segregated in a 1：1 ratio, corresponding to DNA polymorphisms heterozygous in a single parent, and the other 58 loci existing in both parents followed a 3：1 Mendelian segregation ratio. Among the loci with 1：1 segregating ratios, 79 loci were ordered in 14 linkage groups （648.6 cM） of the paternal map, and 72 loci were ordered in 14 linkage groups （601.9 cM） of the maternal map. The average density of loci was approximately 1 per 8 cM. To Investigate the homologies between two parental maps, we used 58 loci segregated 3：1 for further analysis, and deduced one homologous linkage group. The linkage data developed in these maps will be useful for detecting loci-controlling commercially important traits for Laminaria.     

No relation between ACEml/D polymorphism and high altitude pulmonary edema in the Han Chinese

Objectives To explore whether the angiotensin T -converting enzyme （ACE） I/D （insertion/ deletion） polymorphism is associated with the susceptibility to high altitude pulmonary edema （HAPE） in the Han Chinese. Methods One hundred and forty-seven HAPE-p （HAPE patients） and 193 HAPE-r （HAPE resistants） were enrolled from the Yushu earthquake reconstruction workers in Qinghai province where the altitude is over 3 500 m above sea level. Blood samples were collected from each of the HAPE-p and HAPE-r groups. Information about physiological phenotypes was obtained via fieldwork investigation. The ACE-I/D polymorphism in HAPE-p and HAPE-r was detected by polymerase chain reaction （PCR）. Results The SaO2 was significantly lower while HR was significantly higher in HAPE-p group than those in HAPE-r group. The genotype frequencies of ACE-I/D for II, ID, DD in HAPE-r and HAPE-p groups were 0.430, 0.446, 0.124 and 0.435, 0.469, 0.095, respectively, the allelic frequencies of I and D were 0.650, 0.350 and 0.670, 0.330, respectively. The OR of ID, DD and D alleles relative to II for HAPE was 0.961 （0.610-1.514）, 1.322 （0.634-2.758） and 1.080 （0.783-1.489）. There was no significant difference of the genotypic and the allelic frequencies in ACE-I/D polymorphism between HAPE-p and HAPE-r groups. Conclusions There is no relation between ACE-I/D polymorphism and HAPE in the Han Chinese.     

Compensatory foraging in Trinidadian guppies： Effects of acute and chronic predation threats

In response to acute predation threats, prey may sacrifice foraging opportunities in favour of increased predator avoidance. Under conditions of high or frequent predation risk, such tradeoffs may lead to reduced fitness. Here, we test the pre diction that prey reduce the costs associated with lost opportunities following acute predation threats by exhibiting shortterm compensatory foraging responses. Under seminatural conditions, we exposed female guppies Poecilia reticulate from high and low predation risk sites to one of three levels of acute predation threat （high, intermediate or low concentrations of conspecific alarm cues）. Our results confirm previous reports, demonstrating that guppies from a high predation site were consistently ＇bolder＇ （shorter escape latencies） and exhibited graded threatsensitive responses to different simulated threat levels while those from the low predation site were ＇shyer＇ and exhibited nongraded responses. Most importantly, we found that when guppies from low predation sites resumed foraging, they did so at rates significantly lower than baseline rates. However, guppies from high preda tion sites resumed foraging either at rates equal to baseline （in response to low or intemaediate risk stimuli） or significantly in creased relative to baseline rates （in response to high risk stimuli）. Together, these results highlight a complex compensatory be havioral mechanism that may allow prey to reduce the longterm costs associated with predator avoidance [Current Zoology 60 （3）： 323-332, 2014 ].     

A Novel Missense Mutation （L^296Q） in Cholesteryl Ester Transfer Protein Gene Related to Coronary Heart Disease

Cholesteryl ester transfer protein (CETP) is a key participant in the reverse transport of cholesterol from the peripheral tissues to the liver. To understand the role that CETP gene plays in the pathogenesis of coronary heart disease (CHD) , the promoter region, all 16 exons and adjacent intronic regions of CETP gene were screened for single nucleotide polymorphisms (SNPs) in 203 CHD patients and 209 controls by a combination of PCR, denaturing high performance liquid chromatography (DHPLC), molecular cloning, and DNA sequencing. A novel missense mutation in the CETP gene was identified. This mutation (L296Q) was a T-to-A conversion at codon 296 of exon 10 which replaced the codon for leucine (CTG) with the codon for glutamine (CAG). Association study revealed that L296Q mutation was associated with CHD with a significantly higher mutant allele frequency in the CHD patients than that in the controls (0. 160 vs. 0.091,x2= 9.014, P = 0.003), and that the odds ratio for the development of CHD was 1.83 for     

Leukocyte selenium, zinc, and copper concentrations in preeclamptic and normotensive pregnant women

Preeclampsia is an important cause of maternal and perinatal mortality worldwide. The etiology of this relatively common medical complication of pregnancy, however, remains unknown. We studied the relationship between maternal leukocyte selenium, zinc, and copper concentrations and the risk of preeclampsia in a large hospital-based case-control study. One hundred seventy-one women with proteinuric pregnancy-induced hypertension (with or without seizures) comprised the case group. Controls were 184 normotensive pregnant women. Leukocytes were separated from blood samples collected during the patients’ postpartum labor and delivery admission. Leukocyte concentrations for the three cations were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Concentrations for each cation were reported as micrograms per gram of total protein. Women with preeclampsia had significantly higher median leukocyte selenium concentrations than normotensive controls (3.23 vs 2.80 μg/g total protein, p<0.0001). Median leukocyte zinc concentrations were 31% higher in preeclamptics as compared with controls (179.15 vs 136.44 μg/g total protein, p<0.0001). Although median leukocyte copper concentrations were slightly higher for cases than controls, this difference did not reach statistical significance (17.72 vs 17.00 μg/g total protein, p=0.468). There was evidence of a linear increase in risk of preeclampsia with increasing concentrations of selenium and zinc. The relative risk for preeclampsia was 3.38 (adjusted odds ratio [OR]=3.38, 95% confidence interval [CI]=1.53–7.54) among women in the highest quartile of the control selenium distribution compared with women in the lowest quartile. The corresponding relative risk and 95% CI for preeclampsia was 5.30 (2.45–11.44) for women in the highest quartile of the control zinc distribution compared with women in the lowest quartile. There was no clear pattern of a linear trend in risk with increasing concentration of leukocyte copper concentrations (adjusted for linear trend in risk =0.299). Our results are consistent with some previous reports. Prospective studies are needed to determine whether observed alterations in selenium and zinc concentrations precede preeclampsia or whether the differences may be attributed to preeclampsia-related alterations in maternal and fetal-placental trace metal metabolism.     

Association between polymorphism of the cyclin E1 gene and susceptibility to hepatocellular carcinoma in Chinese Han population of Hubei

This study aimed to explore the relationship between CCNE1 gene single nucleotide polymorphisms (SNP rs1406 and rs3218038) and the incidence of hepatitis B virus-related hepatocellular carcinoma (HCC) in the Chinese Han population in Hubei. A total of 663 subjects, including 173 HCC patients, 172 HBV-related liver cirrhosis (LC) patients, 162 asymptomatic HBV carriers (AsC), and 156 healthy controls, participated in the study. Genotyping of CCNE1 rs1406 and rs3218038 polymorphisms was done by illumina second generation sequence method.Our findings showed that rs1406 G>T variant decreased the risk of HCC (OR 0.710, P=0.035 G vs T), and no significant differences were found between rs3218038 SNP and HCC risk using the χ² test. Furthermore, stratified analysis revealed that differences in genotype frequencies were related to gender. Women who carried the CCNE1 GT genotype were significantly associated with a decreased risk of HCC, compared with healthy controls carrying the GG genotype (additive model, OR 0.378,P=0.030).The results suggest that the rs1406 G allele and CCNE1 rs1406 polymorphism produce an increased the risk of HCC in comparison with the T allele. Whereas, the GT genotype is a protective factor in the development of HCC in female patients.     

Low testosterone levels are inversely correlated with carotid artery plaque formation in elderly women

Objective To study the relationship between serum testosterone levels and the plaque formation of the carotid artery in a population-based cohort of independently living healthy women above 60 years of age. Methods Analysis of the healthy elders from a population-based cohort study in 9 communities of Beijing. Carotid intima-media thickness and atherosclerotic plaques were determined ultrasonographically. Serum testosterone levels were measured by immunoassay. The data were analyzed with ANOVA and logistic regression analysis. Results There was an inverse correlation between testosterone and plaque formation in old females（P〈0.01）, while no association was found in males. Female with testosterone levels in the lowest quartile （〈0.49 nmol/L） had more risk of plaque formation（OR=3.805, P〈0.01） after adjusted with age and other traditional factors of atherosclerosis. Conclusion Testosterone concentrations are negatively associated with carotid artery atherosclerosis in old women in Beijing, experimental and prospective studies are needed to determine the possible therapeutic role of testosterone in atherosclerosis.     

Copy number variations of HLA-DRB5 is associated with systemic lupus erythematosus risk in Chinese Han population

Systemic lupus erythematosus （SLE） is a polygenic, systemic, autoimmune disease. Copy number variants （CNVS） have been discovered to be associated with a number of complex disorders. We undertook the current study to explore the potential associations between genomic CNVS and SLE in Chinese Han population. In the discovery stage, seven SLE patients were examined with the high-density comparative genomic hybridization microarrays in the screening test for SLE associated CNVS. Then, in the validation stage, 135 SLE patients and 219 matched healthy subjects were investigated for the CNVS of gene HLA-DRB5 by AccuCopyTM technol- ogy. Quantitative polymerase chain reaction was carried out to determine the copy number （CN） and mRNA level of HLA- DRB5 in SLE patients. Although the mRNA level of HLA- DRB5 between the CN deletion group and the CN normal group in SLE patients was not statistically positive （P = 0.46）, our results still showed more CN of HLA-DRB5 in SLE patients than in healthy controls （P = 3.98×10^-6）. Odds ratio for CN deletion was 0.38 （95% confidence interval （C1）, 0.23-0.61, P = 7.79×10^-5） and for CN duplication was 1.89 （95% CI, 0.56-7.66, P = 0.37）, respectively. These findings indicated that CNVS of HLA-DRB5 was associated with the risk of SLE, and CN deletion appeared to be protective for SLE.     

Polymorphism of Apolipoproteine E in Relation with Alzheimer and Vascular Dementia

Summary 1. The epsilon 4 allele of the apolipoprotein E gene increases the risk of late onset familial and sporadic Alzheimer disease. Relation of epsilon 4 allele of the apolipoprotein E gene to various types of dementia and the onset of dementia were analyzed in the present study.2. The study comprised 139 patients (50 men and 89 women) with dementia, mean age 73.61 years (range 47–98). The diagnosis of dementia was made according to Diagnostic and Statistical Manual of Mental Disorders, and subtypes diagnoses were made according to NINCDS-ADRDA and NINDS-AIREN criteria. Minimental State Examination (MMSE) was used for the screening of dementia. Apolipoprotein E polymorphism was determined by the PCR-RFLP technique-polymerase chain reaction and subsequent digestion with specific restriction endonuclease. For statistical analyses chi-square test and the crude Gart′s odds ratio (OR) and 95% confidence intervals (CI) were used.3. From 139 dementia patients (MMSE ≤24 points) in 61 (45%) Alzheimer disease (AD) was present, in 44 patients (31%) vascular dementia (VD), and in 34 (24%) mixed dementia (MD) were revealed. In comparison with control group the presence of at least one ApoE-ɛ4 allele was significantly higher only in the group with AD (p < 0.001), (OR=2.76; 95%: 1.42–5.36). The frequency of ɛ4 allele carriers was significantly overrepresented in AD group compared with VD (χ²=5.94; p=0.0148). Differences between AD and MD or VD and MD were not confirmed.     

A Matrilineal Genetic Legacy from the Last Glacial Maximum Confers Susceptibility to Schizophrenia in Han Chinese

Mitochondrial dysfunction has been widely reported in schizophrenia patients. To dissect the matrilineal structure of Han Chinese with or without schizophrenia and to decipher the maternal influence and evolutionary history of schizophrenia, a total of 1212 schizophrenia patients and 1005 matched healthy controls, all of Han Chinese origin, were recruited in Hunan Province, China. We classified haplogroup for each individual based on mitochondrial DNA （mtDNA） sequence variations and compared the haplogroup distribution pattern between cases and controls. Haplogroup B5a presented a higher frequency in cases than in controls （P = 0.02, OR = 1.67, 95% CI = [1.09, 2.56]）, and this result could be confirmed by permutation analysis. Age estimation of haplogroup B5a in cases revealed a much younger age than that of controls, which was coincident with the Northern Hemisphere deglaciation at the end of the Last Glacial Maximum. Analysis of complete mtDNA in five patients belonging to haplogroup B5a showed that this background effect might be caused by haplogroup- defining variants m.8584G〉A and m.10398A〉G. Our results showed that matrilineal risk factor for schizophrenia had an ancient origin and might acquire a predisposing effect on schizophrenia due to the environment change and/or orchestration with other nuclear genetic factors appeared recently in human evolutionary history.     

Human leukocyte antigen-DP loci are associated with the persistent infection of hepatitis B virus in Chinese population

A genome-wide association study recently showed that genetic variants in human leukocyte antigen (HLA)-DP loci were strongly associated with a risk of persistent infection of hepatitis B virus (HBV) in Japanese and Thai individuals and variants in interleukin 28B (IL-28B) have been associated with responses to anti-hepatitis C virus (HCV) treatment. The aim of this study was to investigate whether the HLA-DP loci and IL-28B were associated with different outcomes of chronic HBV infection (CHB) in Chinese subjects. The rs9277535 near HLA-DPB1,rs3077 near HLA-DPA1, and rs12979860 genotype near IL28B were genotyped by direct sequencing in 185 CHB patients and 193 self-limited hepatitis B virus (SLHBV)-infected subjects who recovered from HBV infection. The rs9277535 near HLA-DPB1 was strongly associated with CHB (P=0.0000181, OR=1.905). This association was observed independent of HBV e antigen (HBeAg) status and HBV viral loads in HBeAg-positive patients (P=0.0004, OR=1.956), in HBeAg-negative patients (P=0.0009, OR=1.857), and in HBeAg-negative individuals without detectable levels of HBV DNA in serum (P=0.0011, OR=2.05). The rs3077 near HLA-DPA1 was associated with CHB (P=0.0206, OR=0.6865) and HBeAg-positive infection status (P=0.0143, OR=0.6047). Meanwhile, a genetic variation of insertion-deletion (INDEL) polymorphism (rs361527, -/ATAAATGTTGA) near HLA-DPA1 was found to be associated with CHB (P=0.0307, OR=0.7028) and HBeAg-positive CHB infection status (P=0.0233, OR=0.619). However,the rs12979860 genotype near IL28B had no correlation with CHB. This study demonstrated that in the Han Chinese populations, HLA DP loci, but not IL-28B, was associated with persistence of infection in different outcomes of HBV infected patients; however, the mechanism needs to be further investigated.