Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia?
Jung‐Jin KimBrian H. ShirtsMadhulika DayalSilviu‐Alin BacanuJoel WoodWeiting XieXiaohua Douglas ZhangKodavali V. ChowdariRobert H. YolkenBernie DevlinVishwajit L. Nimgaonkar
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Abstract:
Published data support genetic variants, as well as certain infectious agents, as potential risk factors for schizophrenia. Less is known about interactions between the risk factors.To evaluate exposure to infectious agents and host genetic variation as joint risk factors.We investigated four infectious agents: cytomegalovirus (CMV), herpes simplex viruses 1 and 2 (HSV1, HSV2), and Toxoplasma gondii (TOX). We initially compared exposure using specific serum antibodies, among simplex and multiplex nuclear families (one or more than one affected offspring, respectively). If interactions between infectious agents and host genetic variation are important risk factors for schizophrenia, we reasoned that they would be more prominent among multiplex versus simplex families. We also evaluated the role of variation at chromosome 6p21-p23 in conjunction with exposure. We used 22 short tandem repeat polymorphisms (STRPs) dispersed across this region.Though exposure to all four agents was increased among multiplex families versus simplex families, the difference was consistently significant only for CMV (odds of exposure to CMV in multiplex families: 2.47, 95% CI: 1.48-5.33). Transmission disequilibrium tests and case-control comparisons using STRPs revealed significant linkage/association with D6S2672 among CMV+ schizophrenia patients.Polymorphisms near D6S2672 could confer risk for schizophrenia in conjunction with CMV exposure.Keywords:
Cytomegalovirus
To explore the effects of combined CYP1A1 Msp1 genotypes with Ile/Val genotypes on susceptibility to lung cancer. Msp1 and Ile/Val genotypes of CYP1A1 gene were detected with the methods of PCR RFLP and allele specific amplification(ASA) in a case control study,including 92 cases of lung cancer and 98 hospital controls. Msp1 polymorphism site:The risk of lung cancer with the individuals of genotype B or genotype C was 1 85 times greater than that with the individual of genotype A ( χ 2=4 36,P0 05,OR=1 85,95% CI 1 04～3 30 ).Ile/Val polymorphism site:The risk of lung cancer of the individuals with genotype Val/Val was 3 3 times greater than the individual with genotype Ile/Ile ( χ 2=4 12,P0 05,OR=3 3,95% CI 1 02～10 72 ).The lung cancer risks of individuals with combined Ile/Ile genotype and A genotype were compared with these of individuals combined Ile/Val genotype and B ( χ 2=5 81,P0 05,95% CI 1 7～9 96 ),the individuals combined Ile/Val genotype and C genotype ( χ 2=4 74,P0 05,95% CI 1 11～20 9 ) and the individuals combined Val/Val genotype and C genotype ( χ 2=4 42,P0 05,95% CI 1 27～23 6 ). [Conclusion] The genotype C and genotype Val/Val of CYP1A1 gene may be susceptible to lung cancer,the individuals with two susceptible genotypes were more susceptible to lung cancer.
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Objective
To investigate the current distribution of hepatitis C virus (HCV) genotype in Southern China and to understand the HCV transmission and to infer its transmitting trend.
Methods
The HCV gene subtypes of 3 524 specimens from Southern China were detected and analyzed by polyonerase chain reaction (PCR)-fluorescence probe method or sequencing. The regular nested PCR and sequencing were used for the phylogenetic tree analysis when the fluorescence PCR inefficiently identifying virus isolates.
Results
Among 3 524 specimens, there were 2 922 cases from Guangdong, 78 cases from Fujian, 152 cases from Hainan and 372 cases from Guangxi. Genotype 1b comprised the majority (1 808/3 524, 51.3%), followed by genotype 6a (925/3 524, 26.2%), 2a (298/3 524, 8.46%), 3a (246/3 524, 6.98%), 3b (200/3 524, 5.68%) and 1a (27/3 524, 0.77%). In addition, 1 case was genotype 6e, 1 case was genotype 6q, 1 case was genotype 6r, 3 case were genotype 6w, 2 case were genotype 6xa, 2 case were genotype 6n, and 1 case was genotype 6 with unclassified subtype. The genotype 1b accounted for the majority in most areas of 21 cities and counties in Guangdong Province, followed by genotype 6a. But in some areas, the major genotype was genotype 6a, followed by 1b. Genotype 4, genotype 5 and genotype 7 were not found in this study.
Conclusions
In the past two years, genotype 1b and 6a are still the epidemic genotypes in Guangdong, Guangxi and Hainan provinces. However, genotype 6a has replaced 1b as the dominant one in some areas in Guangdong Province. The distributions of HCV genotypes do not change significantly in Guangxi and Fujian provinces.
Key words:
Southern China; Hepatitis C virus; PCR- fluorescent probe method; Genotype distribution; Phylogenetic tree
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【Objective】To investigate the main genotype of hepatitis B virus carrier in Lasa.【Methods】 The S gene were amplified by PCR from the HBsAg positive patients in Tibet.After sequencing the end-labelled PCR production,the gene sequences were compared with the registered standard genotype sequences in GenBank. 【Results】 Of the 60 specimens,46(76.7%) could be detected directly,among them 14 were genotype B(5 were minority),12 were genotype C(5 were minority) and 20 were genotype D(3 were minority).14 specimens which undetected might be mixed genotype.【Conclusion】 Genotype B,C,D and mixed type are detected in Lasa,the dominant genotype of HBV is D in this area,but genotype A and E are not found.
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NS5B
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[Objective] To investigate genotype and subtype of hepatitis B virus in 2 counties(districts) of Sichuan province.[Methods] Virus DNA were extracted from samples both positive for HBsAg and HBeAg.After polymerase reaction(PCR) and sequencing of partial S gene,genotypes and subtypes were analysized by phylogenetic analysis and deduced amino acid sequences,respectively.[Results] Of 49 samples,those with w subdeterminant and those with r subdeterminant be-longed exclusively to genotype B and genotype C,respectively;31 samples were genotype B/subtype adw2,1 was genotype B/subtype ayw1,1 was genotype B/subtype adw3,14 were genotype C /subtype adrq+,and 2 were genotype C /subtype ayr.[Conclusion] Genotype B /subtype adw2 and genotype C/subtype adrq+ accounted for most proportion,and genotype B/sub-type adw2 predominated in 2 counties(districts);rare genotype B/subtype adw3 also existed.
HBeAg
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Objective To investigate the distribution of genotypes of hepatitis B virus(HBV) in Sichuan.Methods With PCR type-specific primers combined with sequencing of genotype,we investigated the gene of HBV in the serum of 500 hepatitis B patients in Sichuan.Results The distribution of HBV-DNA genotype of 500 patients included genotype A(3 cases,0.6%),genotype B(284,cases,56.8%),genotype C(186,cases,37.2%),genotype D(7,cases,0.8%),genotype B+C(12 cases,2.4%) and genotype C+D(6 cases,1.2%).Conclusion The HBV genotype is correspond with genotypes in other area in our country.
Hepatitis B
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Objective To detect the polymorphism of CYP1A1-MspI gene in patients with ovarian cancer.and discuss the relationship between the polymorphism ofCYP1A1-MspI gene and correspond cases' general materials and clinical materials.Methods The free peripheral blood samples of 81 cases confirmed to be ovarian cancer by postoperative pathology were collected preoperatively and the polymorphism of CYP1A1-MspI gene was detected.The clinical materials of the 81 cases with different genotypes were compared.The relationship between the polymorphism and clinical materials was analyzed.Results Among the 81 cases of ovarian cancer,there were 47 cases of wild type-genotype A(T/T)(58%),25 cases of mutation heterozygosis-genotype B(T/C)(31%),and 9 cases of mutation homozygosis-genotype C(C/C)(11%).The genotypic frequency distribution in patients aged from 12 to 29 was one case of genotype A(2.1%),5 cases of genotype B(20.0%),and no case of genotype C.The genotypic frequency distribution in patients aged from 30 to 49 was 12 case of genotype A(25.5%),8 cases of genotype B(32.0%),and 3 cases of genotype C(33.3%).The genotypic frequency distribution in patients aged from 50 to 69 was 31 case of genotype A(66.0%),8 cases of genotype B(32.0%) and 4 cases of genotype C(44.4%).The genotypic frequency distribution in patients aged more than 70 years was 3 case were of genotype A(6.4%),4 cases of genotype B(16.0%),2 case of genotype C(22.2%).There were significant differences of the ages of onset between patients with different CYP1A1-MspI genotypes (P0.05).There were 40 cases of genotype A(85.1%),15 cases of genotype B(60.0%),and 9 cases of genotype C(100%) in epithelial cancer patients.There significant differences of the constituent ratio of the ovarian cancer pathological types between patients with different genotypes(P0.05).Conclusion Polymorphism of CYP1A1-MspI gene exisits in patients with ovarian cancer.The age of onset of patients with ovarian cancer is related with CYP1A1-MSPI genotypes;The incidence of epithelium tumor in patients with genotype A is higher than that of other ones.The ratio of non-epithelial tumor in the patients with mutation allele gene C has an increasing tendency.
Genotype frequency
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We examined the natural course and clinical characteristics of 138 HCV carriers according to HCV genotypes. Stored serum samples obtained from patients were examined for HCV core antigen levels and HCV genotypes. Genotype 1b was found in 79 (57.2%), genotype 2a in 8 (5.8%), genotype 2b in 46 (33.3%) and genotype 1b+2b in 5 (3.6%) patients.119 patients followed 20 years or more after infection excluding genotype 1b+2b were classified into two groups : genotype 1b and non-genotype 1b (2a and 2b : 2a/2b). The numbers of patients were 70 and 49 in the genotype 1b and genotype 2a/2b groups, respectively. Patients with genotype 2a/2b had significantly higher HCV core antigen levels 20 years after infection than those with genotype 1b. However, patients with genotype 1b had significantly higher ZTT and type IV collagen than those with genotype 2a/2b.HCV core antigen levels in cases with genotype 1b did not increase 10 years or more after infection ; on the other hand, those with genotype 2a/2b increased significantly.
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Parvovirus B19 comprises three distinct genotypes (1, 2, and 3). The distribution of B19 genotypes has not before been examined in South Africa. Two hundred thirty-nine laboratory samples submitted to a diagnostic virology laboratory for parvovirus DNA detection were analyzed retrospectively. Of the 53 PCR-positive samples investigated, 40 (75.4%) were identified as genotype 1 by genotype-specific PCR or consensus NS1 PCR and sequencing and 3 (5.7%) as genotype 2 and 10 (18.9%) as genotype 3 by analysis of NS1 sequences. Furthermore, phylogenetic analysis identified two genotype 1 sequences which were distinct from the previously described genotypes 1A and 1B. Interestingly, a genotype 2 virus was detected in the serum of an 11-year-old child, providing evidence for its recent circulation. This is the first study to demonstrate the concurrent circulation of all three genotypes of B19 in South Africa and the provisional identification of a novel subtype of genotype 1. The implications of parvovirus B19 variation are discussed.
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ABSTRACT Combinations of 10 Cryptosporidium parvum oocysts, with various ratios of genotype I to genotype II, were isolated and subjected to PCR-restriction fragment length polymorphism analysis. Amplification of both genotypes in these samples ranged from 31 to 74% and yielded no information about the genotype proportions. In addition, since both genotypes were not always detected, amplification of a single genotype is not conclusive evidence that the sample contains only a single genotype.
Cryptosporidium parvum
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