Association In Chinese Population Research Articles

Anti-Mitotic Spindle Apparatus Antoantibodies: Prevalence and Disease Association in Chinese Population.

Mitotic spindle apparatus (MSA) antibodies are rare findings with undefined clinical significance in clinical research. We aimed at investigating the prevalence and clinical significance of anti-MSA antibodies in Chinese population. Between 2008 and 2013, a total of 180,180 patients were studied for the presence of anti-MSA antibodies. The clinical details and laboratory data of anti-MSA-positive patients were retrospectively collected and analyzed. Of the 180,180 patients tested, 68,640 patients presented with positive antinuclear antibodies (ANAs, 38.10%), but only 32 patients with positive anti-MSA antibodies (0.018%). Diagnoses were established in 22 of 32 patients: 16 connective tissue diseases (CTDs), mainly Sjogren syndrome (SS, 5/16), rheumatoid arthritis (RA, 4/16), and systemic lupus erythematosus (SLE, 3/16), and 6 nonautoimmune conditions. The most frequent clinical symptoms of the anti-MSA-positive patients were arthralgia and eyes and mouth drying. Additionally, 70% of anti-MSA antibodies were not associated with other ANAs, however, when associated, the most frequent ANA was anti-SSA. Anti-MSA antibodies have a low prevalence and female gender predominance. Anti-MSA antibodies are primarily associated with CTDs, mainly SS, RA, and SLE. The presence of anti-MSA antibodies might be the unique serological markers of the CTDs, especially when anti-SSA, SSB, and dsDNA antibodies are negative, or the level of RF is low.

Association of interleukin 3 (IL-3) polymorphisms with schizophrenia in Han Chinese population

Schizophrenia has been observed to be associated with various abnormalities in multiple cytokines. Recent genetic analyses showed that the interleukin 3 (IL-3) gene and its receptors are significantly associated with schizophrenia, especially in Irish populations. To examine the associations of the Irish-risk single nucleotide polymorphisms (SNPs, e.g., rs3916441) in the IL-3 gene with schizophrenia in Chinese population, we utilized two independent samples from Southwestern China, including a total 901 schizophrenia patients and 1417 healthy controls. However, no statistically significant differences were observed in allelic or genotypic frequencies of the tested 6 SNPs in IL-3 between cases and controls in any sample. Therefore, the results of our analyses were not able to confirm the association of IL-3 SNPs with schizophrenia. The absence of the IL-3’s association in Chinese population suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating associations of schizophrenia across different ethnic populations.

CR1 rs3818361 Polymorphism Contributes to Alzheimer's Disease Susceptibility in Chinese Population.

Recent genome-wide association studies (GWAS) reported CR1 rs3818361 polymorphism to be an Alzheimer's disease (AD) susceptibility variant in European ancestry. Three independent studies investigated this association in Chinese population. However, these studies reported weak or no significant association. Here, we reinvestigated the association using all the samples from three independent studies in Chinese population (N = 4047, 1244AD cases and 2803 controls). We also selected three independent studies in European ancestry population (N = 11787, 3939AD cases and 7848 controls) to evaluate the effect of rs3818361 polymorphism on AD risk in different ethnic backgrounds. In Chinese population, we did not identified significant heterogeneity using additive, recessive, and dominant genetic models. Meta-analysis showed significant association between rs3818361 and AD with P = 6.00E-03 and P = 5.00E-03. We further identified no heterogeneity of rs3818361 polymorphism between Chinese and European populations. We found that rs3818361 polymorphism contributed to AD with similar genetic risk in Chinese and European populations. In summary, this is the first study to show significant association between rs3818361 polymorphism and AD in Chinese population by a meta-analysis method. Our findings indicate that the effect of CR1 rs3818361 polymorphism on AD risk in Chinese cohorts is consistent with the increased risk observed in European AD cohorts.

How genome-wide SNP-SNP interactions relate to nasopharyngeal carcinoma susceptibility.

This study is the first to use genome-wide association study (GWAS) data to evaluate the multidimensional genetic architecture underlying nasopharyngeal cancer. Since analysis of data from GWAS confirms a close and consistent association between elevated risk for nasopharyngeal carcinoma (NPC) and major histocompatibility complex class 1 genes, our goal here was to explore lesser effects of gene-gene interactions. We conducted an exhaustive genome-wide analysis of GWAS data of NPC, revealing two-locus interactions occurring between single nucleotide polymorphisms (SNPs), and identified a number of suggestive interaction loci which were missed by traditional GWAS analyses. Although none of the interaction pairs we identified passed the genome-wide Bonferroni-adjusted threshold for significance, using independent GWAS data from the same population (Stage 2), we selected 66 SNP pairs in 39 clusters with P<0.01. We identified that in several chromosome regions, multiple suggestive interactions group to form a block-like signal, effectively reducing the rate of false discovery. The strongest cluster of interactions involved the CREB5 gene and a SNP rs1607979 on chromosome 17q22 (P = 9.86×10−11) which also show trans-expression quantitative loci (eQTL) association in Chinese population. We then detected a complicated cis-interaction pattern around the NPC-associated HLA-B locus, which is immediately adjacent to copy-number variations implicated in male susceptibility for NPC. While it remains to be seen exactly how and to what degree SNP-SNP interactions such as these affect susceptibility for nasopharyngeal cancer, future research on these questions holds great promise for increasing our understanding of this disease’s genetic etiology, and possibly also that of other gene-related cancers.

XRCC1 Arg399Gln polymorphism contributes to increased risk of colorectal cancer in Chinese population

Previous studies investigating the association between X-ray repair cross-complementation group 1 (XRCC1) Arg399Gln polymorphism and colorectal cancer risk in Chinese provided inconsistent findings. To assess the association in Chinese population, a meta-analysis was performed. Eligible studies were searched in Pubmed, Emabse, and China National Knowledge Infrastructure databases. Odds ratios (OR) with the corresponding 95 % confidence intervals (95 %CI) were pooled to assess the association. Seven case-control studies involving a total of 2136 colorectal cancer cases and 3168 controls were finally included in the meta-analysis. Our analysis suggested that the variant genotypes of XRCC1 Arg399Gln were associated with an increased risk of colorectal cancer in Chinese population (Gln vs. Arg: random effect model OR = 1.24, 95 %CI = 1.01-1.52, P = 0.041; GlnGln vs. ArgArg: random effect model OR = 1.52, 95 %CI = 1.07-2.15, P = 0.019; and Recessive model: fixed effect model OR = 1.37, 95 %CI = 1.12-1.67, P = 0.002). There was low risk of publication bias in present meta-analysis. Our meta-analysis provides an evidence for the association between XRCC1 Arg399Gln polymorphism and colorectal cancer risk in Chinese population, and XRCC1 Arg399Gln variant genotypes contribute to increased risk of colorectal cancer in Chinese.

Association between polymorphisms of XRCC1 and ADPRT genes and ovarian cancer survival with platinum-based chemotherapy in Chinese population

The role of DNA repair gene polymorphisms in cancer development, progression, and response to treatment has received increased attention. We conducted a prospective study to determine whether associations exist between two polymorphisms in XRCC1 and ADPRT and the outcomes of Chinese ovarian cancer patients treated with platinum-based chemotherapy. A total of 335 new cases of ovarian cancer were consecutively collected between May 2005 and May 2007. Follow-up lasted for 4 years, and the outcome measure was survival time. Individuals carrying XRCC1 194Trp/Trp had a longer survival time than did those with the Arg/Arg genotype. Similarly, those carrying XRCC1 399 Gln/Gln genotypes had 0.44-fold the risk of death than those with the Arg/Arg genotype. The combination of XRCC1 194 Trp allele and 399 Gln allele could decrease the death risk of ovarian cancer. In summary, this study is the first to evaluate the associations between polymorphisms in DNA repair gene polymorphism and the risk of ovarian cancer in Chinese population. Our study found a significant association between XRCC1 Arg399Gln and XRCC1 Arg194Trp polymorphism and the clinical outcome of ovarian cancer. Furthermore, studies with larger sample sizes are still needed to confirm these associations in Chinese population.

Genetic variants of the PITX3 gene are not associated with late-onset sporadic Parkinson's disease in a Chinese population

PITX3 is a transcription factor which determines the survival of dopaminergic neurons in the substantia nigra, and is considered a candidate gene for Parkinson's disease (PD). Recent association studies indicated that three PITX3 single nucleotide polymorphisms (SNPs), including rs2281983, rs4919621, and rs3758549 are likely to be associated with PD. However, no similar associations in Chinese populations have been reported. To examine the nature of the association in Chinese individuals we analyzed DNA samples for these three PITX3 SNPs from 509 late-onset sporadic PD patients, and 494 healthy controls, using a ligase detection reaction (LDR). Results indicated that allele and genotype frequencies did not differ between patients and controls for all three SNPs, suggesting that these SNP sites do not contribute to the risk of developing PD in late-onset sporadic PD in this Chinese population.

Non-invasive screening of HLA-DPA1 and HLA-DPB1 alleles for persistent hepatitis B virus infection: Susceptibility for vertical transmission and toward a personalized approach for vaccination and treatment

BackgroundPolymorphisms in the major histocompatibility complex (MHC) and non-MHC genes were recently reported to be associated with persistent hepatitis B virus (HBV) infection and host response to hepatitis B vaccine in Asian populations. We aimed to confirm the associations in Chinese population and develop a non-invasive screening method for the risk loci. MethodsWe genotyped 2 risk alleles on the MHC loci, HLA-DPA1 (rs3077) and HLA-DPB1 (rs9277535), and 1 risk allele near a non-MHC gene, FOXP1 (rs6789153) using high-resolution melting curve analysis. With minimal processing steps and time, salivary DNA was extracted with a modified protocol of a blood kit. We compared the genotyping fidelity between peripheral blood DNA and salivary DNA. ResultsBoth rs3077 and rs9277535, but not rs6789153, are significantly associated with CHB in Chinese population (p-value<0.001). High genotype concordance between different sources of genomic DNA was obtained. ConclusionsGenotyping salivary DNA using our modified methods provides a non-invasive fast screening for host susceptibility loci. The transmission mechanism of hepatitis B can now be modified by adding genetic susceptibility to the traditional vertical transmission model of hepatitis B.

XRCC1 gene polymorphisms and esophageal squamous cell carcinoma risk in Chinese population: A meta‐analysis of case–control studies

Two non-synonymous polymorphisms Arg194Trp and Arg399Gln in the DNA-base excision repair gene X-ray repair cross-complementing group 1 (XRCC1) have been implicated in risk for esophageal cancer. However, the results from different studies remain controversial. The present meta-analysis of literatures was performed to clarify these associations in Chinese population. A comprehensive literature search was conducted to identify all case-control studies of XRCC1 polymorphisms Arg194Trp and Arg399Gln and risk for esophageal squamous cell carcinoma (ESCC). A total of 9 eligible studies, including 1,538 ESCC cases and 2,472 controls, were identified to the meta-analysis. The odds ratio (OR) for the variant homozygous genotype Trp/Trp of the Arg194Trp polymorphism, compared with the wild-type homozygote Arg/Arg, was 1.59 (p = 0.0007), with 95% confidence interval (95% CI) 1.22-2.09, for ESCC risk without between-study heterogeneity. However, there was no statistically significant associations of ESCC risk in the dominant model Arg/Trp+Trp/Trp (OR 0.97; 95% CI 0.84-1.12; p = 0.69) and heterozygous genotype Arg/Trp (OR 0.90; 95% CI 0.77-1.04; p = 0.16) when comparing with wild-type genotype Arg/Arg. For Arg399Gln, there was no effect in dominant modeling (Arg/Gln+Gln/Gln vs. Arg/Arg: OR 0.92; 95% CI 0.80-1.06; p = 0.25), and the variant Gln/Gln homozygote was not associated with ESCC risk (OR 1.29; 95% CI 0.79-2.10; p = 0.31), either. In conclusion, Arg194Trp genetic polymorphism may be associated with an increased risk for developing ESCC and a study with the larger sample size is needed to further evaluate gene-environment interaction on XRCC1 polymorphisms and ESCC risk.

Single-nucleotide polymorphisms of mismatch repair genes in healthy Chinese individuals and sporadic colorectal cancer patients

Mismatch repair (MMR) genes are among of the most important genes associated with colorectal cancer (CRC). Single-nucleotide polymorphisms (SNPs) are generally thought to provide important information across a wide spectrum of life sciences; however, no study of association between SNPs of MMR genes and Chinese sporadic colorectal cancer (SCRC) is available. We chose 29 reported single-nucleotide variants that have rarely been verified in a population-based study. We identified SNPs and the genotype–phenotype association in Chinese populations of 150 healthy individuals and 160 SCRC patients. We extracted the genomic DNA from the blood of these individuals and used sequencing to determine these SNPs. Three SNPs ( MLH1 394G→C, 655A→G, 1151T→A) occurred with a frequency of 8.8–11.2% in the Chinese population. These SNPs formed a series with combined effects. The haplotype of concurrent MLH1 655 and 1151 SNPs and the haplotype combinations of MLH1 1151, MLH1 394 occurred exclusively in SCRC. None of the other 26 variants were detected in the Chinese population.