The association between microRNA polymorphisms and the risk of childhood acute lymphoblastic leukemia: A meta-analysis

The aim of this meta-analysis was to determine the relationship between microRNA polymorphisms and the risk of childhood acute lymphoblastic leukemia comprehensively. PubMed, EMBASE, Scopus, Web of Science, the Cochrane Library, Global Index Medicus, Clinicaltrials.gov, ProQuest, and Open Grey databases were used to find relevant papers. Using the STATA 16.0 and CMA 3.0 software, the significance of relationships between microRNA polymorphisms and childhood acute lymphoblastic leukemia risk was evaluated using odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for five genetic models. The results of the meta-analysis showed that there was no significant association between the polymorphism of miR-146a rs2910164 and childhood acute lymphoblastic leukemia risk in different genetic models. Also, in the sensitivity analysis, removing Xue's study from the analysis indicated that both the homozygote and recessive models are significantly affected. Additionally, there was a statistically significant relationship between the polymorphisms of pri-miR-34b/c rs4938723 (in the homozygote and recessive models) and miR-612 rs12803915 (in the allele and dominant models) and childhood acute lymphoblastic leukemia risk. These findings suggest that the rs4938723 and rs12803915 polymorphisms may have a role in the development of childhood acute lymphoblastic leukemia.     

CXCL12 and TP53 genetic polymorphisms as markers of susceptibility in a Brazilian children population with acute lymphoblastic leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Genetic polymorphisms in the 3′UTR region of the CXCL12 (rs1801157) and TP53 codon 72 (rs1042522) genes may contribute to susceptibility to childhood ALL because they affect some important processes, such as metastasis regulation and tumor suppression. Thus the objective of the present study was to detect the frequency of two genetic polymorphisms in ALL patients and controls and to add information their impact on genetic susceptibility and prognosis. The CXCL12 and TP53 polymorphisms were tested in 54 ALL child patients and in 58 controls by restriction fragment length polymerase chain reaction and allelic specific chain reaction techniques, respectively. The frequencies of both allelic variants were higher in ALL patients than in the controls and indicated a positive association: OR = 2.44; 95 % CI 1.05–5.64 for CXCL12 and OR = 2.20; 95 % CI 1.03–4.70 for TP53. Furthermore, when the two genetic variants were analyzed together, they increased significantly more than fivefold the risk of this neoplasia development (OR = 5.24; 95 % CI 1.39–19.75), indicating their potential as susceptibility markers for ALL disease and the relevance of the allelic variant combination to increased risk of developing malignant tumors. Future studies may indicate a larger panel of genes involved in susceptibility of childhood ALL and other hematological neoplasias.     

Association of ATM and BMI‐1 genetic variation with breast cancer risk in Han Chinese

We tested the hypothesis that genetic variation in ATM and BMI‐1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer‐free controls of Han nationality. This was an observational, hospital‐based, case–control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy‐Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene were significantly higher in cases than in controls (P = .005, <.001 and .001, respectively). Two variants, rs1042059 and rs201024480, in BMI‐1 gene were low penetrant, with no detectable significance. After adjustment, rs189037 and rs1801516 were significantly associated with breast cancer under the additive model (OR: 1.37 and 1.52, 95% CI: 1.10‐1.71 and 1.14‐2.04, P: .005 and .005, respectively). In haplotype analysis, haplotypes A‐C‐G‐G (in order of rs189037, rs3092856, rs1801516 and rs373759) and A‐C‐A‐A in ATM gene were significantly associated with 1.98‐fold and 6.04‐fold increased risk of breast cancer (95% CI: 1.36‐2.90 and 1.65‐22.08, respectively). Nomogram analysis estimated that the cumulative proportion of 3 significant variants in ATM gene was about 12.5%. Our findings collectively indicated that ATM gene was a candidate gene in susceptibility to breast cancer in Han Chinese.     

Association between promoter variants of interleukin-18 and schizophrenia in a Han Chinese population

An increasing amount of evidence suggests that interleukin-18 (IL-18) plays a pivotal role in the pathophysiology of schizophrenia. However, association between single nucleotide polymorphism of IL-18 and the risk of schizophrenia has not been clarified. This study examined whether two promoter polymorphisms -137 G/C (rs187238) and -607 C/A (rs1946518) of IL-18 were associated with schizophrenia and six clinical symptoms (disorder of perception, thought disorder, disturbance of emotion, disorder of behavior and volition, suicide action, and aggressive action) to provide data for screening high-risk Han Chinese individuals. Three hundred seventy-two schizophrenic patients and 353 healthy controls from a Han Chinese population were examined to assess their genotype and allele frequencies of the two promoter polymorphisms of IL-18. The genotype distributions in both patients and controls were within Hardy-Weinberg equilibrium. No significant differences were observed in the genotype or the allele frequencies of the two single-nucleotide polymorphisms between patients and controls. However, genotype frequencies of -607 C/A showed significant differences between patients and controls in the appearance of perception disorder (χ2 = 6.153, p = 0.046). A significant difference was detected in -137 G/C between patients and controls in the appearance of aggressive action (χ2 = 3.909, p = 0.048). In conclusion, IL-18 gene promoter polymorphisms may not contribute to the susceptibility of schizophrenia in a Han Chinese population, but two single-nucleotide polymorphisms, -137 G/C and -607 C/A, may play a role in the development of perception disorder and aggressive action, respectively.     

Contribution of Polymorphisms in IKZF1 Gene to Childhood Acute Leukemia: A Meta-Analysis of 33 Case-Control Studies

Objective

Two common polymorphisms in the IKZF1 gene (rs4132601 and rs11978267 variants) have been reported to be associated with childhood acute leukemia (AL) risk, however the results were inconsistent. Here, we conducted a meta-analysis to generate large-scale evidence on whether IKZF1 variants are risk factors for childhood AL.

Methods

The PubMed, Embase, EBSCO, and Web of Science were searched up to June 2, 2014 for studies on the association of IKZF1 polymorphisms with childhood AL risk. Data were extracted and the odd ratios (ORs) and95% confidence intervals (95% CIs) were calculated by a fixed-effects orrandom-effects model. Subgroup analysis by ethnicity and leukemia subtype, sensitivity and cumulative meta-analyses were performed. Moreover, publication bias was assessed by Begg''s and Egger''s tests.

Results

In total, 33 case control studies were finally included in this meta-analysis. For rs4132601 polymorphism, significantly increased AL risk was observed in all genetic models (the association was still significant when the p value was Bonferroni adjusted to 0.025). In the subgroup analysis by tumor type, statistical association was observed in B-cell precursor ALL (BCP-ALL). Additionally, when stratified by ethnicity, significantly increased AL risk was only observed in European subgroup, but not among African or mixed population subgroups. Finally, similar results were found forrs11978267 polymorphism.

Conclusion

In summary, this meta-analysis provides evidence that rs4132601 and rs11978267 polymorphisms in the IKZF1 gene mightcontribute to the occurrence of BCP-ALL, especially in European populations. Moreover, further studies with large sample size are required to clarify possibleroles of IKZF1 variants in other ethnic groups (e.g., Asians and Africans).     

Association between the Polymorphism rs3217927 of CCND2 and the Risk of Childhood Acute Lymphoblastic Leukemia in a Chinese Population

CyclinD proteins, the ultimate recipients of mitogenic and oncogenic signals, play a crucial role in cell-cycle regulation. CyclinD2, one of the cyclinD family, is overexpressed in T-acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia and involved in the pathogenesis of leukemias. Recent reports indicated that CCND2 polymorphisms are associated with human cancer risk, thusly we hypothesized that CCND2 gene polymorphisms may contribute to childhood ALL susceptibility. We selected the polymorphism rs3217927 located in the 3′UTR region of CCND2 to assess its associations with childhood ALL risk in a case-control study. A significant difference was found in the genotype distributions of rs3217927 polymorphism between cases and controls (P = 0.019) and homozygous GG genotype may be an increased risk factor for childhood ALL (adjusted OR  =  1.84, 95% CI  =  1.14 —2.99). Furthermore, this increased risk was more pronounced with GG genotype among high-risk ALL (adjusted OR  = 1.95, 95% CI  =  1.04–3.67), low-risk ALL (adjusted OR  =  2.09, 95% CI  =  1.13–3.87), B-phenotype ALL patients (adjusted OR  =  1.78, 95% CI  =  1.08–2.95) and T-phenotype ALL patients (adjusted OR  =  2.87, 95% CI  =  1.16–7.13). Our results provide evidence that CCND2 polymorphism rs3217927 may be involved in the etiology of childhood ALL, and the GG genotype of rs3217927 may modulate the genetic susceptibility to childhood ALL in the Chinese population. Further functional studies and investigations in larger populations should be conducted to validate our findings.     

Genetic polymorphisms of the DNA repair geneMPG may be associated with susceptibility to rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. A previous study indicated that a DNA repair system was involved in the development of RA. In this study, we investigated the association of four N-methylpurine-DNA glycosylase (MPG) gene polymorphisms (rs3176364, rs710079, rs2858056, and rs2541632) with susceptibility to RA in 384 Taiwanese individuals (192 RA patients and 192 control subjects). Our data show a statistically significant difference in genotype frequency distributions at rs710079 and rs2858056 SNPs between RA patients and control groups (P = 0.040 and 0.029, respectively). Our data also indicated that individuals with the GG genotype at rs2858056 SNP may have a higher risk of developing RA. In addition, compared with the haplotype frequencies between case and control groups, individuals with the GCGC haplotype appeared to be at a greater risk of RA progression (P = 0.003, OR = 1.75; 95% CI = 1.20-1.55). Our results suggest that rs710079 and rs2858056 polymorphisms and the GCGC haplotype in the MPG gene are associated with the risk of RA progression, and thus may be used as molecular markers of RA if they are confirmed by further research.     

CYP3A5 and NAT2 gene polymorphisms: role in childhood acute lymphoblastic leukemia risk and treatment outcome

Susceptibility to acute lymphoblastic leukemia can be highly influenced by genetic polymorphisms in metabolizing enzyme genes of environmental carcinogens. This study aimed to evaluate the impact of the CYP3A5 and NAT2 metabolizing enzyme polymorphisms on the risk of childhood acute lymphoblastic leukemia. The analysis was conducted on 204 ALL patients and in 364 controls from a Brazilian population, using PCR-RFLP. The CYP3A5 3 polymorphic homozygous genotype was more frequent among ALL patients and the 3 allele variant was significantly associated with increased risk of childhood ALL (OR = 0.29; 95% CI, 0.14-0.60). The homozygous polymorphic genotype for the 6 allele variant was extremely rare and found in only two individuals. The heterozygous frequencies were similar for the ALL group and the control group. No significant differences were observed between the groups analyzed regarding NAT2 variant polymorphisms. None of the polymorphisms analyzed was related to treatment outcome. The results suggest that CYP3A5 3 polymorphism may play an important role in the risk of childhood ALL.     

Association of pre-microRNAs genetic variants with susceptibility in systemic lupus erythematosus

MicroRNAs (miRNAs) may play important roles in SLE, but genetic polymorphisms of miRNAs and their relationships with various autoantibodies present in SLE patients remain unclear. Here, we report that 213 SLE patients and 209 healthy individuals of Chinese had been taken into this case–control studies, which had been performed by selecting two miRNAs (hsa-mir-146a rs2910164 G>C, and hsa-mir-499 rs3746444 T>C) to analyze the genetic polymorphisms. The single nucleotide polymorphism (SNP) variants had been analyzed by PCR–RFLP and serum anti-ribonucleoprotein (anti-RNP), anti-Sm nuclear antigen (anti-Sm) antibodies had been determined by an anti-ENA kit and serum anti-double-stranded DNA (anti-dsDNA) antibodies had been assessed by indirect immunofluorescence. We found that hsa-mir-146a rs2910164 and hsa-mir-499 rs3746444 polymorphisms had no significant relationship with SLE susceptibility. The genotype frequencies of rs2910164 (GG, CC, and GC) were 16, 37, and 47% in SLE patients, but 11, 39, and 50% in healthy group (P = 0.397), respectively; The genotype frequencies of rs3746444 (CC, TT, and TC) were 3, 74, and 23% in SLE patients, but 3, 76, and 22% in healthy group (P = 0.892), respectively. The G and C allele frequencies of rs2910164 were 39 and 61% in SLE patients, but 36 and 64% in healthy group (P = 0.990), respectively. The C and T allele frequencies of rs3746444 were 15 and 85% in SLE patients, but 14 and 86% in healthy group (P = 0.702), respectively. In addition, we also showed no significant difference in the distribution of rs2910164 and rs3746444 genotypes in each of the three antibodies (anti-RNP, anti-Sm, and anti-dsDNA).     

Correlation between TICAM1 gene polymorphisms and community‐acquired pneumonia in children

This study aims to explore the relationship between single nucleotide polymorphisms (SNPs) of the TICAM1 gene and community‐acquired pneumonia (CAP) in Chinese children. The polymorphisms of eight tag SNP (TagSNP) locus of TICAM1 were detected using the improved multiplex ligation detection reaction (iMLDR) assay in 375 children with CAP (average age, 37.8 ± 21.6 months) and 306 healthy children (average age, 38.5 ± 23.8 months). The correlation between polymorphisms of these TagSNPs and the risk, severity, sepsis, and CRP level of childhood CAP were evaluated using logistic regression analysis. The CC genotype of rs11466711T/C locus of TICAM1 is correlated with childhood CAP susceptibility, which significantly reduced the risk of childhood CAP (P < .05), The AA genotype of the rs6510826G/A locus and haplotype CCCA were associated with CRP level in childhood CAP, which significantly increased the risk of CRP increase (P < .05 and P < .01, respectively), The AA genotype of rs35747610G/A site is associated with sepsis in childhood CAP, significantly reduced risk of sepsis (P < .05). While the haplotype CCCG of this locus led to a significant reduction in the risks of childhood CAP, severe pneumonia and pneumonia sepsis (all P < .05). TICAM1 has multiple functional variants closely related to the development and progression of childhood CAP, and these variations may have a synergistic effect on the development of childhood CAP.     

广西壮族人群EBI3 基因rs6613A/T, rs4905A/G多态性分布特点

目的:分析广西壮族人群EBI3基因rs6613A/T、rs4905A/G多态性分布特点。方法:采用单碱基延伸的PCR技术对168例广西壮族人群EBI3 rs6613 A/T和EBI3 rs4905A/G进行多态性检测,对比国际人类基因组计划(Hap Map)公布的中国北京人、日本人、非洲人和意大利人的SNP分型数据,分析5个人群rs6613 A/T、rs4905A/G位点的基因型和等位基因频率差异。结果:在广西壮族人群中,EBI3基因rs6613 A/T位点AT基因型最常见,约为49.4%;T等位基因频率最高,约为52.1%;rs4905A/G多态性位点AC基因型最常见,约为48.2%;C等位基因频率最高,约为50.9%。EBI3基因型及等位基因频率分布于性别无显著相关性(P0.05)。广西壮族人群EBI3基因rs6613A/T位点基因型和等位基因频率与北京人差异无统计学意义(P0.05),但与非洲人、日本人、意大利人差异具有统计学意义(P0.05);EB-13基因rs4905A/G位点基因型和等位基因频率与北京人和日本人差异无统计学意义(P0.05),但与非洲人和意大利人比较差异具有统计学意义(P0.01)。结论:EBI3基因rs6613 A/T和EB-13 rs4905A/G多态性位点基因型和等位基因在广西壮族人群中的分布频率与其他种族和地区人群相比存在差异,这种差异可能是导致某些疾病在不同人群发病率和临床表现存在差异的原因之一。     

SNP Association Mapping across the Extended Major Histocompatibility Complex and Risk of B-Cell Precursor Acute Lymphoblastic Leukemia in Children

The extended major histocompatibility complex (xMHC) is the most gene-dense region of the genome and harbors a disproportionately large number of genes involved in immune function. The postulated role of infection in the causation of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) suggests that the xMHC may make an important contribution to the risk of this disease. We conducted association mapping across an approximately 4 megabase region of the xMHC using a validated panel of single nucleotide polymorphisms (SNPs) in childhood BCP-ALL cases (n=567) enrolled in the Northern California Childhood Leukemia Study (NCCLS) compared with population controls (n=892). Logistic regression analyses of 1,145 SNPs, adjusted for age, sex, and Hispanic ethnicity indicated potential associations between several SNPs and childhood BCP-ALL. After accounting for multiple comparisons, one of these included a statistically significant increased risk associated with rs9296068 (OR=1.40, 95% CI=1.19-1.66, corrected p=0.036), located in proximity to HLA-DOA. Sliding window haplotype analysis identified an additional locus located in the extended class I region in proximity to TRIM27 tagged by a haplotype comprising rs1237485, rs3118361, and rs2032502 (corrected global p=0.046). Our findings suggest that susceptibility to childhood BCP-ALL is influenced by genetic variation within the xMHC and indicate at least two important regions for future evaluation.     

A Promoter polymorphism (rs17222919, -1316T/G) of ALOX5AP is associated with intracerebral hemorrhage in Korean population

To investigate whether single nucleotide polymorphisms (SNPs) of eicosanoid biosynthesis genes are associated with intracerebral hemorrhage (ICH) and ischemic stroke (IS), seven SNPs in the coding or promoter regions were selected: ALOX12 (rs434473, Asn322Ser), ALOX5 (rs2228064, Thr90Thr), ALOX5AP (rs17222919, -1316T/G), PTGES (rs7872802, -404A/G), PTGIS (rs5628, Leu256Leu), PTGS1 (rs3842788, Gln41Gln) and PTGS2 (rs5275, 3'UTR). A total of 398 control subjects and 196 stroke patients (79 ICH and 117 IS) were genotyped by direct sequencing. The rs17222919 SNP was associated with ICH in codominant 1 (P=0.008), dominant (P=0.003) and log-additive (P=0.004) models. Allele frequencies of rs17222919 were different between ICH and controls (P=0.007). However, the seven tested SNPs were not associated with clinical phenotypes (NIHSS, MBI and CRPS) in ICH and IS. These results suggest that the promoter SNP rs17222919 of ALOX5AP may be associated with the development of ICH in Korean population.     

Genetic polymorphisms and haplotypes of the organic cation transporter 1 gene (SLC22A1) in the Xhosa population of South Africa

Human organic cation transporter 1 is primarily expressed in hepatocytes and mediates the electrogenic transport of various endogenous and exogenous compounds, including clinically important drugs. Genetic polymorphisms in the gene coding for human organic cation transporter 1, SLC22A1, are increasingly being recognized as a possible mechanism explaining the variable response to clinical drugs, which are substrates for this transporter. The genotypic and allelic distributions of 19 nonsynonymous and one intronic SLC22A1 single nucleotide polymorphisms were determined in 148 healthy Xhosa participants from South Africa, using a SNAPshot^® multiplex assay. In addition, haplotype structure for SLC22A1 was inferred from the genotypic data. The minor allele frequencies for S14F (rs34447885), P341L (rs2282143), V519F (rs78899680), and the intronic variant rs622342 were 1.7%, 8.4%, 3.0%, and 21.6%, respectively. None of the participants carried the variant allele for R61C (rs12208357), C88R (rs55918055), S189L (rs34104736), G220V (rs36103319), P283L (rs4646277), R287G (rs4646278), G401S (rs34130495), M440I (rs35956182), or G465R (rs34059508). In addition, no variant alleles were observed for A306T (COSM164365), A413V (rs144322387), M420V (rs142448543), I421F (rs139512541), C436F (rs139512541), V501E (rs143175763), or I542V (rs137928512) in the population. Eight haplotypes were inferred from the genotypic data. This study reports important genetic data that could be useful for future pharmacogenetic studies of drug transporters in the indigenous Sub-Saharan African populations.     

Association of HHIP polymorphisms with COPD and COPD-related phenotypes in a Chinese Han population

The hedgehog signaling pathway plays an important role in lung morphogenesis and cellular responses to lung injury. Genome-wide association studies (GWAS) and integrative genomics approaches have demonstrated the associations between HHIP polymorphisms and chronic obstructive pulmonary disease (COPD) and in non-Asian populations. Here we investigated whether HHIP polymorphisms would also be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population. In the present case–control study a total of 680 COPD patients and 687 healthy control subjects were recruited. Six single nucleotide polymorphisms (SNPs) (rs1828591, rs13118928, rs6817273, rs10519717, rs12504628, rs13147758) were selected for genotyping. Allele frequencies and genotype distributions were compared between patients and controls. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested by using logistic regression analysis. Association between haplotypes and COPD outcome was also assessed. We identified that SNP rs12504628 was associated with FEV1/FVC ratio among cases (P = 0.0460). Moreover, the HHIP SNP rs10519717 was associated with the severity of disease (adjusted P-value = 0.0300). The six SNPs showed strong linkage disequilibrium (r² ≥ 0.9). Three major haplotypes were observed but showed no significant difference between case and control groups (P = 0.4532, 0.0875, and 0.3484, respectively). In conclusion, our study suggests that the HHIP gene may be involved in COPD susceptibility in Chinese Han population.     

Interleukin 4 receptor is associated with an increase in body mass index in Koreans

A body of evidence indicates obesity is an inflammatory state with chronic activation of the immune system. The interleukin 4 receptor (IL4R) single nucleotide polymorphism (SNP), rs 180275 (1902A>G) is well recognized for its association with atopy and other inflammatory diseases. We assessed the possible association of rs 180275 and rs 1805010 with obesity in Korean population. Study subject consisting of 876 Koreans were divided into three groups: subjects with 1) BMI<25, 2) BMI between 25 and 27, and 3) BMI>27. Analyses of genotype distributions and allele frequencies of study subjects revealed that rs 180275 polymorphism was associated with an increase in BMI in Korean population (P=0.009 and 0.011, respectively) while no association was found between rs 1805010 and obesity. We observed significantly lower percentage of rs 180275 G allele in subjects with BMI>27 than in subjects with BMI< or =27 (9.9% vs. 16.0%). Logistic regression analysis revealed that the odds ratio (OR) for an increase in BMI associated with the G vs. A allele was 0.57 [95% Confidence interval (CI)=0.39-0.85, p=0.002], which strongly implicates the protective role of rs 180275 G allele against an increase in BMI. Haplotype analysis revealed no association was present between rs 180275 and rs 1805010 polymorphisms. The frequency of rs 180275 G allele is significantly lower in subjects with BMI>27, suggesting the protective role of IL4R rs 180275 G allele against an increase in BMI in Korean population.     

FOXO3 gene polymorphisms influence the risk of acute lymphoblastic leukemia in Chinese children

Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed cancer in children and single-nucleotide polymorphisms (SNPs) in certain genes influence risk of ALL. Although FOXO3 had been demonstrated to be involved leukemia, the role of FOXO3 polymorphisms was still not clear. In the present study, we explored the association of FOXO3 SNPs with ALL risk in Chinese children. We genotyped four polymorphisms (rs17069665 A>G, rs4945816 T>C, rs4946936 C>T, and rs9400241 A>C) of FOXO3 in 425 ALL cases and 1339 health controls. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Further analyses were performed to explore associations of rs17069665 and rs9400241 with ALL susceptibility in terms of age, gender, immunophenotype, minimal residual disease (MRD), and other clinical characteristics. We found rs17069665 related to the increased ALL risk (OR = 1.76; 95% CI = 1.02-3.04), rs9400241 related to decreased ALL risk (OR = 0.80; 95% CI = 0.64-0.99). The effects of rs17069665 on ALL risk were more predominant in males and children < 10 years, and patients with lower rates of platelet or neutrophil. As for rs9400241, the effects were more predominant in children < 10 years, and in patients with pre B ALL, positive MRD, anemia, or hepatomegaly. In conclusion, FOXO3 gene polymorphisms influence the risk of ALL in children and might be a potential biomarker for ALL susceptibility.     

The IL6 gene polymorphism -634C>G and IL17F gene polymorphism 7488T>C influence bone mineral density in young and elderly Japanese women

Osteoporosis is an important public health problem because of the significant morbidity and mortality associated with its complications, particularly fractures. An important clinical risk factor in the pathogenesis of osteoporosis is the presence of genetic polymorphisms in susceptibility genes. However, few studies have investigated the relevance of these polymorphisms in premenopausal women. Recent studies have demonstrated interactions between bone and immune cells, and that cytokines produced by immune cells regulate bone turnover. In this study, we examined the associations between bone mineral density (BMD) and polymorphisms in genes encoding interleukin (IL)-6 (-634C>G; rs1800796), tumor necrosis factor (TNF)-α (-308G>A; rs1800629), IL-17F (7488T>C; rs763780), transforming growth factor (TGF)-β (869T>C; rs1800470), osteoprotegerin (OPG; 163A>G; rs3102735) and methylenetetrahydrofolate reductase (MTHFR; 677C>T; rs1801133) in young and elderly Japanese women. Whole-body, lumbar spine (L(1) or L(2)-L(4)), and femoral neck BMD were measured in 100 young subjects (18-23 years), and 100 elderly subjects (60-83 years). Whole-body, lumbar spine, and femoral neck BMD were 1.13±0.06, 1.14±0.12, and 1.00±0.11 g/cm(2), respectively, in young subjects, and 0.92±0.09, 0.86±0.15, and 0.63±0.10 g/cm(2), respectively, in elderly subjects. The frequencies of the IL-6 CC, CG, and GG genotypes were 48%, 49%, and 3%, respectively. The frequencies of the IL17F TT, TC, and CC genotypes were 79%, 15%, and 6%, respectively, in young subjects. Polymorphisms of the IL-6 and IL17F genes were significantly associated with BMD. To our knowledge, this is the first report to examine these associations in a cohort of 200 Japanese women.     

Hepatocyte Growth Factor Genetic Variations and Primary Angle-Closure Glaucoma in the Han Chinese Population

Purpose

The aim of this study is to examine whether or not hepatocyte growth factor (HGF) genetic variations are associated with susceptibility to primary angle-closure glaucoma (PACG) in the Han Chinese population.

Methods

Three single-nucleotide polymorphisms (SNPs)–rs5745718, rs17427817, and rs3735520–in the HGF gene were genotyped in 238 adult patients with PACG and 287 age-, sex-, and ethnically matched healthy controls by using a polymerase chain reaction restriction fragment length polymorphism assay. Data was analyzed by χ² analysis.

Results

The three tested analyzed polymorphisms in the HGF gene were in Hardy-Weinberg equilibrium, in all the subjects. The frequencies of the genotype and allele of rs5745718 and rs1742817 in the HGF gene were significantly different between the PACG patients and the controls. On one hand, the frequencies of the CC genotype and C allele of rs5745718 were significantly decreased in PACG patients compared with controls (P_c = 1.40×10⁻³; P_c = 3.21×10⁻⁴, respectively); however, on the other hand, significantly decreased frequencies of the GG genotype and the G allele of rs17427817 were observed in PACG patients compared with the controls (P_c = 0.006,; P_c = 6.06×10⁻⁴, respectively). A comparison of the distributions of the genotypes and alleles of rs3735520 showed no statistically significant differences between the PACG patients and the controls (p_c>0.05). The haplotype analysis results showed that the CGC haplotype frequency was significantly decreased in the patients with PACG compared with the controls (p_c<0.001). No difference was detected between the patients and the controls with regard to the other haplotypes.

Conclusions

Our study suggests that rs5745718 and rs17427817 are associated with a decreased risk of PACG in the Chinese Han population. The CGC haplotype was demonstrated to possibly play a protective role against PACG in this population.