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Background Most susceptible loci of hepatocellular carcinoma (HCC) identified by genome-wide association studies (GWAS) are located in non-coding regions, and the mechanism of action remains unclear. The objective of this study was to explore the association of single nucleotide polymorphisms (SNPs) on long non-coding RNAs (lncRNAs) that affect competing endogenous RNAs (ceRNA) regulation mechanism with the risk and prognosis of HCC. Methods Based on a set of bioinformatics strategies, eight lncRNA genes that affect HCC through the mechanism of lncRNA-mediated ceRNA were systematically screened, and 15 SNPs that affect microRNA (miRNA) binding in these lncRNA genes were annotated. Genotyping was performed in 800 HCC cases and 801 healthy controls to examine associations of these SNPs with HCC in a northeastern Chinese Han population. Results The GG, GC and GG + GC genotypes of HOTAIR rs7958904 were associated with a 0.65, 0.59 and 0.63-fold decreased HCC risk, respectively. In addition, HCC patients with PVT1 rs3931282 AA + GA genotypes were less prone to develop late-stage cancers in a stratified analysis of clinical characteristics. When stratified by clinical biochemical indexes, rs1134492 and rs10589312 in PVT1 and rs84557 in EGFR-AS1 showed significant associations with aspartate aminotransferase (AST), alanine aminotransferase (ALT) or AST/ALT ratio in HCC patients. Furthermore, we constructed potential ceRNA regulatory axes that might be affected by five positive SNPs to explain the causes of these genetic associations. Conclusions HOTAIR rs7958904, PVT1 rs3931282, rs1134492 and rs10589312, and EGFR-AS1 rs84557 might be predictors for HCC risk or prognosis. Our results provide new insights into how SNPs on lncRNA-mediated ceRNAs confer interindividual differences to occurrence and progression of HCC.

Background and Aims. Men who have sex with men (MSM) are at high risk of HIV infection. The nonhomologous end joining (NHEJ) pathway is the main way of double-stranded DNA break (DSB) repair in the higher eukaryotes and can repair the DSB timely at any time in cell cycle. It is also indicated that the NHEJ pathway is associated with HIV-1 infection since the DSB in host genome DNA occurs in the process of HIV-1 integration. The aim of the present investigation was to evaluate associations of single-nucleotide polymorphisms (SNPs) in NHEJ pathway genes with susceptibility to HIV-1 infection and AIDS progression among MSM residing in northern China. Methods. A total of 481 HIV-1 seropositive men and 493 HIV-1 seronegative men were included in this case-control study. Genotyping of 22 SNPs in NHEJ pathway genes was performed using the SNPscan™ Kit. Results. Positive associations were observed between XRCC6 rs132770 and XRCC4 rs1056503 genotypes and the susceptibility to HIV-1 infection. In gene-gene interaction analysis, significant SNP-SNP interactions of XRCC6 and XRCC4 genetic variations were found to play a potential role in the risk of HIV-1 infection. In stratified analysis, XRCC5 rs16855458 was significantly associated with CD4+ T cell counts in AIDS patients, whereas LIG4 rs1805388 was linked to the clinical phases of AIDS patients. Conclusions. NHEJ gene polymorphisms can be considered to be risk factors of HIV-1 infection and AIDS progression in the northern Chinese MSM population.

Background DAL-1 gene was reported to inhibit proliferation, migration, invasion, and epithelial to mesenchymal transition (EMT) of gastric cancer (GC) cells in our previous study. The association between the genomic variants in DAL-1 gene with risk of GC is still unclear. Methods In this study, 505 GC cases and 544 healthy controls (HCs) were collected to evaluate the association between six single nucleotide polymorphisms (SNPs) (rs7240736, rs73937194, rs3817466, rs8082898, rs73381527, rs9953490) of DAL-1 gene and GC risk in the Han population in Northeast China. Results The TA + AA genotypes of rs9953490 were significantly associated with an increased risk in N3 compared with N0 subgroup (adjusted OR = 4.56, 95% CI = 1.49–13.98, P = 0.008), and also showed evident association with an increased risk in TNM stage III compared with stage I-II (adjusted OR = 2.33, 95% CI = 1.16–4.67, P = 0.017). Conclusion The rs9953490 of DAL-1 gene may play an important role in the occurrence and development of GC in the Han population in Northeast China.

BACKGROUND Previous studies reported that DNA damage repair (DDR) genes may play an important role in HIV-1 infection. The MRE11 gene, a member of the MRN complex, plays an essential part in the homologous recombination pathway, which is one of the classical DDR pathways. Previous reports have demonstrated that MRE11 has an effect on HIV-1 replication. However, the role of SNPs in the MRE11 gene and their impact on HIV-1 infection and AIDS progression remain unknown. METHODS In this study, 434 MSM HIV-1-infected patients in northern China and 431 age-matched healthy controls were enrolled. Five SNPs (rs2155209, rs10831234, rs13447720, rs601341 and rs11020803) at the MRE11 gene were genotyped. Another series of cases (409 MSM HIV-1-infected patients) and controls (403 age-matched healthy males) were recruited as the validation set. RESULTS In our study, rs10831234 showed differences in allele frequencies between cases and controls (P = 0.005). Additionally, there was an association between rs10831234 and HIV-1 infection susceptibility in dominant and additive models (P = 0.005 and P = 0.006, respectively). All significant associations were replicated in the validation set, and the associations were still significant after Bonferroni correction for multiple testing when the two data sets were combined. Furthermore, in haplotype association analyses between the case and control groups, the frequencies of the haplotypes Crs11020803Crs10831234 and Trs11020803Trs10831234 showed significant differences (P = 0.0181 and P = 0.0068, respectively). CONCLUSIONS We demonstrated that the MRE11 rs10831234-T allele may confer increased risk of HIV-1 infection.

Objectives: The relationship between Noggin ( NOG) and methylenetetrahydrofolate reductase and nonsyndromic cleft lip and palate (NSCLP) has been reported participate in craniofacial development but need further evidence. To indicate the susceptibility between the 2 genes and NSCLP, rs227731 and rs1801131 polymorphisms were included in the present research. This research may provide some genetic clues for disease detection and surveillance. Design: Seventeen studies including 4023 cases and 5691 controls were provided for meta-analysis, and odds ratio (OR) with 95% CI were obtained to estimate NSCLP risk. Results: Our analysis suggested potential association of rs227731C on increasing the risk of NSCLP in the Caucasian group and total group but not Asian group under all models: allele (OR = 1.45, 95% CI = 1.21-1.75, P < .0001), homozygote (OR = 2.03, 95% CI = 1.42-2.90, P < .0001), heterozygote (OR = 1.44, 95% CI = 1.19-1.73, P = .0001), dominant (OR = 1.61, 95% CI = 1.27-2.04, P < .0001), and recessive models (OR = 1.63, 95% CI = 1.25-2.12, P = .0003). Besides, increased risk is related to rs1801131 in Asian group under 3 models: allele (OR = 1.24, 95% CI = 1.06-1.44, P = .006), heterozygote (OR = 1.24, 95% CI = 1.02-1.52, P = .03), and dominant models (OR = 1.29, 95% CI = 1.06-1.56, P = .009). Conclusions: Our analysis indicates polymorphisms rs227731 and rs1801131 are associated with NSCLP, with predominance of different ethnic group and deepen understanding of NSCLP.

Background: Prenatal intake of folic acid is important for prevention of NSCL/P (nonsyndromic cleft lip with or without cleft palate). Associated genes in folate pathway are major enzymes of folic acid metabolism that is crucial for preventing birth defects. The present meta-analysis aims to investigate the association between four SNPs in folate pathway genes and the risk of NSCL/P. Methods: Comprehensive bioinformatics analysis was used to predict the functional pathogenicity of genetic variation. The PubMed, Embase database and Google Scholar were searched by two researchers. Stata 11.0 software was used to analyze the results. Subgroup analysis was carried out to assess the influence of genetic background. Sensitivity analysis, regression analysis and publication analysis were also conducted to enhance the strength of our results. Results: It is estimated that the probability of two missense mutation rs1801133 in MTHFR and rs1801394 in MTRR are more likely to be damaging by bioinformatics analysis. A significant association between rs1801133 and risk of NSCL/P in two genetic models: TT genotype vs CC genotype (OR = 1.333 95%CI = 1.062–1.674, P = 0.013), and recessive model (OR = 1.325 95%CI = 1.075–1.634, P = 0.008). A significant protective association between rs1801394 GG genotype and NSCL/P in Asian (GG vs AA, OR = 0.520 95%CI = 0.321–0.841, P = 0.008) was observed. Meta-regression, sensitivity analysis, and publication bias analysis confirmed that the results of the present study were statistically significant. Conclusions: The present study identified that rs1801133 in MTHFR is associated with the risk of NSCL/P, and rs1801394 GG genotype in MTRR play a protective role in Asian. Further, larger studies should be performed to confirm these findings.

Background Heilongjiang Province located in northeast China is a multi-ethnic region with people who have lived in cold conditions for several generations. Fatty acids are important to people with cold resistance. CPT1A encodes a protein that imports long-chain fatty acids into the mitochondria for fatty-acid oxidation. FADS is an essential enzyme for the synthesis of long-chain polyunsaturated fatty acids. Results In the present study, we investigated the distributions of three cold resistance-related SNPs (rs80356779 G > A in CPT1A, rs7115739 T > G in FADS3 and rs174570 C > T in FADS2) from six populations that included 1093 individuals who have lived in Heilongjiang Province for at least three generations. The frequencies of rs174570 and rs7115739 were different in our six north minorities compared to the Chinese Dai in Xishuangbanna (CDX) in southern China. All the SNPs in Hezhen were significantly different from other five studied populations. In addition, the genetic distribution of rs174570 in Daur was significantly different from Manchu and Korea, and the frequency of rs7115739 in Ewenki was significantly different from the other populations. The results also showed that the frequencies of the three SNPs in the six minorities were different from those of Greenlandic Inuit and Siberian population. Conclusions Our results showed the distributions of the three cold resistance-related SNPs from six populations that included 1093 individuals in northern China. Distributions of the allele frequencies for the cold resistance-related SNPs in northern China were statistically different from those in southern China. These data help to establish the DNA genome database for the six populations and fully preserve existing minority genetic information. Electronic supplementary material The online version of this article (10.1186/s12864-018-4524-1) contains supplementary material, which is available to authorized users.

Tumor necrosis factor-α (TNF-α) is involved in insulin resistance and has long been a candidate gene implicated in type 2 diabetes mellitus (T2DM), however the association between TNF-α polymorphisms -308G/A and -238G/A and T2DM remains controversial. The present study sought to verify associations between these polymorphisms and T2DM susceptibility using a meta-analysis approach. A total of 49 case–control studies were selected up to October 2018. Statistical analyses were performed by STATA 15.0 software. The odds ratios (ORs) and 95% confidence intervals were calculated to estimate associations. Meta-analyses revealed significant associations between TNF-α −308G/A and T2DM in the allele model (P=0.000); the dominant model (P=0.000); the recessive model (P=0.001); the overdominant model (P=0.008) and the codominant model (P=0.000). Subgroup analyses also showed associations in the allele model (P=0.006); the dominant model (P=0.004) and the overdominant model (P=0.005) in the Caucasian and in the allele model (P=0.007); the dominant model (P=0.014); the recessive model (P=0.000) and the codominant model (P=0.000) in the Asian. There were no associations between TNF-α −238G/A and T2DM in the overall and subgroup populations. Meta-regression, sensitivity analysis and publication bias analysis confirmed that results and data were statistically robust. Our meta-analysis suggests that TNF-α −308G/A is a risk factor for T2DM in Caucasian and Asian populations. It also indicates that TNF-α −238G/A may not be a risk factor for T2DM. More comprehensive studies will be required to confirm these associations.

Psoriasis is a chronic immune-mediated disease with a complex etiology involving various genetic and immunological factors as well as environmental factors. Psoriasis is thought to be mediated by T-cells polarized to a Th17 fate. PTPN2 encodes the T-cell protein tyrosine phosphatase, which acts as a negative regulator of the JAK/STAT signaling pathways downstream of cytokines and plays a prominent role in T-cell activation, signaling and/or effector function. To evaluate the association between PTPN2 gene polymorphisms and psoriasis in the Northeastern Chinese population. A case-control study was conducted, and 398 patients with psoriasis and 397 healthy controls were genotyped for thirteen genetic polymorphisms in PTPN2. Allele analysis revealed that rs2847297, rs657555 and rs482160 polymorphisms were significantly associated with psoriasis (p = 0.0018, p = 0.0017 and p = 0.0086, respectively). Genotype analysis also revealed that these polymorphisms were significantly associated with psoriasis under different models (codominant, dominant and recessive models) (p 0.05). In this study, three haplotypes (H1, H7 and H11) were also found to be associated with psoriasis (p = 0.0015, p = 0.0094, and p = 0.0124, respectively). These results indicate that PTPN2 genetic polymorphisms are associated with psoriasis in the Northeastern Chinese population.

The objective of the study is to assess the association between rs1801278 and rs2943641 of insulin receptor substrate 1 gene (IRS1) and the susceptibility to type 2 diabetes. A literature search strategy was conducted to identify all references lists of relevant studies. The fixed or random effect model was used to calculate the pooled ORs on the basis of heterogeneity. Further analyses were performed to explore the sources of heterogeneity by sensitivity analysis, meta-regression analysis, and subgroup analysis. There was significant association between rs1801278 and type 2 diabetes risk in recessive model (AA vs. GA + GG, p = 0.043) and codominant model (AA vs. GG, p = 0.007). Subgroup analysis showed that the association between rs1801278 and type 2 diabetes risk was significant in dominant model (GA + AA vs. GG, p = 0.044), codominant model (GA vs. GG, p = 0.039), codominant model (AA vs. GG, p = 0.044), overdominant model (GG + AA vs. GA, p = 0.037) in Asian and codominant model (AA vs. GG, p = 0.039) in Caucasian of rs1801278. The association between rs2943641 and type 2 diabetes risk was significant in codominant model (CT vs. CC, p = 0.023) in Caucasian. This meta-analysis suggests that rs1801278 may play a role in type 2 diabetes risk, especially in Asian. It also indicates that rs2943641 may be associated with type 2 diabetes risk in Caucasian. Further larger studies should be performed to warrant confirmation.

It has been reported that DNA repair genes play an important role in HIV-1 infection and AIDS progression. One DNA repair pathway, the mismatch repair (MMR) is associated with a wide variety of tumors. However, the role of single nucleotide polymorphisms (SNPs) in the MMR genes and their importance in HIV-1 infection and AIDS progression remain unclear. In the present study, 479 HIV-1-infected and 487 healthy individuals from northern China were genotyped for nine SNPs in the MSH2 gene (rs13019654, rs4608577, rs4952887, rs6726691, rs10191478, rs12999145, rs1981929, rs2042649, rs2303428) and five SNPs in the MSH6 gene (rs2348244, rs3136245, rs3136329, rs2072447, rs7562048). Our results showed that the rs7562048 G allele frequency was significantly higher in the cases with the CD4+ T-lymphocyte count 200 cells/μl (P = 0.001, OR = 1.811, 95% CI 1.255–2.614), which is in agreement with the result of the Bonferroni correction. The frequencies of the rs2348244 C allele and rs3136245 T allele were higher in the cases at clinical phase IV than those at clinical phase I + II + III (P = 0.026, OR = 1.591, 95% CI 1.056–2.398 and P = 0.019, OR = 1.749, 95% CI 1.096–2.791, respectively); however, this difference is not supported by the Bonferroni correction. There were no significant differences in the frequency of allele, genotype and haplotype of the 14 SNPs between HIV-1-infected individuals and healthy controls (P > 0.05). These results suggest that the rs7562048 is associated with the clinical features and that the MSH6 gene polymorphisms likely play an important role in the progression of AIDS in the northern Chinese population.

Background: A disintegrin and metalloprotease 33 (ADAM33) has recently been suspected to be associated with psoriasis. Objective:To study the association between ADAM33 and psoriasis in the northeastern Chinese Han population. Methods: We genotyped six common single nucleotide polymorphisms from ADAM33 in 400 psoriasis cases and 398 controls using the Multiplex SNaPSHOT method. Results: We observed an increased risk of psoriasis to be associated with the rs2787094CC CG, rs528557CC CG genotypes (p < 0.05) and 3 haplotypes (H1, H3, and H5; p < 0.05). We also found that the rs512625AA rs612709AA GA genotypes and haplotype H8 may be protective against psoriasis (p < 0.05). Among these genotypes, rs2787094CC exhibited the strongest association with psoriasis (OR = 2.537,being the highest OR, p = 0.0014). Conclusions: ADAM33 polymorphisms are associated with psoriasis in the northeastern Chinese Han population.

Several molecular epidemiological studies were conducted in recent years to evaluate the association between NQO1 Pro187Ser polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 3177 cases with breast cancer and 4038 controls from seven published case-control studies showed that the 187Ser allele was not associated with a significantly increased risk of breast cancer (Ser versus Pro: P = 0.33, OR = 1.08, 95% CI = 0.92-1.28; Ser/Ser versus Pro/Pro: P = 0.58, OR = 1.16, 95% CI = 0.68-2.00; Ser/Ser versus Pro/Ser + Pro/Pro: P = 0.62, OR = 1.14, 95% CI = 0.68-1.90; Ser/Ser + Pro/Ser versus Pro/Pro: P = 0.30, OR = 1.07, 95% CI = 0.94-1.22). In the stratified analysis by ethnicity, we found that the Pro187Ser polymorphism was associated with increased breast cancer risk in Caucasians in the additive genetic model and dominant genetic model (P = 0.03, OR = 1.13, 95% CI = 1.01-1.26; P = 0.03, OR = 1.15, 95% CI = 1.01-1.30, respectively), whereas no significant in Asians (P = 0.44, OR = 0.94, 95% CI = 0.80-1.10) and postmenopausal women (P = 0.99, OR = 1.00, 95% CI = 0.84-1.19). The results suggest that NQO1 Pro187Ser polymorphism may contribute to breast cancer development in Caucasians.

It has been reported that single nucleotide polymorphisms (SNPs) in the promoter of the CCR5 gene are associated with the risk for HIV-1 infection and AIDS progression. Using resequencing, we performed a systematic survey of 78 HIV-1 seropositive individuals and 70 population-matched healthy control individuals from northern China to investigate SNPs of the CCR5 gene promoter and evaluated their effects on HIV-1 infection and the progression of AIDS. Linkage disequilibrium (LD) plots and haplotypes were generated using Haploview software. The association analyses were statistically compared using the Chi-square test with SPSS13.0 software for Windows. Seven SNPs (58755A>G, 58791C>T, 58934G>T, 59029A>G, 59353C>T, 59402A>G and 59653C>T) in the region of the CCR5 gene promoter were evaluated in this study. Among the seven SNPs, the minor allele frequencies of 58755G and 58791T were less than 2%. The differences in frequencies of the other five SNPs were not significant between case and control cohorts (P > 0.05). In the case cohort, the association between these SNPs and clinical features (CD4+ T-lymphocyte counts and clinical categories) was not significant (P > 0.05); however, there was a significant association between the haplotype GGTAC and susceptibility to HIV-1 infection (P < 0.05), which is not consistent with other reports studied in different populations. The results suggest that the haplotype GGTAC may have a role in the process of HIV-1 infection in the northern Chinese population.

Background Congenital cataract is a Mendelian disorder that frequently causes blindness in infants. To date, various cataract-associated loci have been mapped; more than 30 genes have been identified by linkage analysis. However, the pathogenic loci in some affected families are still unknown, and new research strategies are needed. In this study, we used linkage-exome combinational analysis to further investigate the pedigree of a four-generation Chinese family with autosomal dominant coralliform cataract. Methods We combined whole exome sequencing and linkage analysis to identify the causative mutation. The exome capture and next-generation sequencing were used to sequence the protein-coding regions in the genome of the proband to identify rare mutations, which were further screened for candidate mutations in linkage regions. Candidate mutations were independently verified for co-segregation in the whole pedigree using Sanger sequencing. Results We identified a C to A transversion at nucleotide position c.70 in exon 2 of CRYGD, a cataract-associated gene. This mutation resulted in a threonine substitution for proline at amino acid residue 24. Conclusions We identified a missense P24T mutation in CRYGD that was responsible for coralliform cataract in our studied family. Our findings suggest that the combination of exome sequencing and linkage analysis is a powerful tool for identifying Mendelian disease mutations that might be missed by the classic linkage analysis strategy.

Hepatocyte nuclear factor 1β (HNF1β), a transcription factor encoded by the transcription factor 2 gene (TCF2), plays a critical role in pancreatic cell formation and glucose homeostasis. It has been suggested that single nucleotide polymorphisms (SNPs) of TCF2 are associated with susceptibility to type 2 diabetes (T2D). However, published results are inconsistent and inclusive. To further investigate the role of these common variants, we examined the association of TCF2 polymorphisms with the risk of T2D in a Han population in northeastern China. We genotyped five SNPs in 624 T2D patients and 630 healthy controls by using a SNaPshot method, and evaluated the T2D risk conferred by individual SNPs and haplotypes. In the single-locus analysis, we found that rs752010, rs4430796 and rs7501939 showed allelic differences between T2D patients and healthy controls, with an OR of 1.26 (95% CI 1.08–1.51, P = 0.003), an OR of 1.23 (95% CI 1.06–1.55, P = 0.001) and an OR of 1.28 (95% CI 1.10–1.61, P = 0.001), respectively. Genotype association analysis of each locus also revealed that the homozygous carriers of the at-risk allele had a significant increased T2D risk compared to homozygous carriers of the other allele (OR 1.78, 95% CI 1.20–2.64 for rs752010; OR 1.82, 95% CI 1.24–2.67 for rs4430796; OR 1.95, 95% CI 1.31–2.90 for rs7501939), even after Bonferroni correction for multiple comparisons. Besides, the haplotype-based analysis demonstrated that AGT in block rs752010-rs4430796-rs7501939 was associated with about 30% increase in T2D risk (OR 1.31, 95% CI 1.09–1.57, P = 0.01). Our findings suggested that TCF2 variants may be involved in T2D risk in a Han population of northeastern China. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.

Variants in the gene encoding transcription factor 7-like 2 (TCF7L2) are associated with type 2 diabetes mellitus (T2D) in several ethnic groups. Two intronic variants, rs290487 and rs11196218, were originally identified as T2D modifiers in Hong Kong Chinese and Taiwan Chinese populations, respectively. However, discrepancies were noted in subsequent replicated studies. In this study, an association of these two loci with T2D was investigated in a Harbin Chinese population. Whereas the two populations in the initial studies were southern Han Chinese, Harbin Chinese are from northeastern China. The SNPs rs290487 and rs11196218 were genotyped by ligase detection reactions in 700 T2D patients and 570 unrelated non-diabetic controls. Association analyses, which were carried out using the case-control sample set, yielded a significant association between rs290487 and T2D, with a trend opposite to that described in a previous report. Specifically, rs290487T was found to be significantly associated with disease susceptibility (p = 0.039), and the allelic OR of rs290487T carriers was 1.184 (95% CI 1.008–1.391). There was no significant association between rs11196218 and T2D. Taken together, TCF7L2 may be an important susceptibility gene for T2D in some Chinese populations. The discrepancies in the allelic associations determined for northern vs. southern Chinese allude to the presence of genetic variation among the Han Chinese.

The association between multiple sclerosis (MS) and tumor necrosis factor-alpha gene (TNF-α) polymorphisms has been analyzed in several studies, but conflicting results have been reported. The main purpose of this study was to integrate previous findings and explore whether the three single nucleotide polymorphisms (SNPs; -238G/A, -308G/A, and -376G/A) of TNF-α are associated with susceptibility to MS. A total of 2,639 patients and 3,303 controls from 21 studies, which were identified by searching the ISI Web of Knowledge database and the PubMed database up to December 2009, were collected for this meta-analysis. The association between MS and TNF-α -238G/A, -308G/A, and -376G/A was previously analyzed in 4, 18, and 4 studies, respectively. Overall, no associations were identified for the TNF-α -238G/A polymorphism and MS in any of genetic model. Similarly, no associations were found for the TNF-α -308G/A polymorphism and MS or between the TNF-α -376G/A polymorphism and MS. Furthermore, no significant association between the three SNPs and MS was identified using subgroup analyses examining ethnicity and clinical manifestation. The results of the present study indicated that TNF-α -238G/A, -308G/A, or -376G/A may not be the main risk factor for MS, which should be interpret with caution for the limited study numbers.