Diagnostic and prognostic role of serum glypican 3 in patients with hepatocellular carcinoma

α‐Feto protein (AFP) is the widely used tumor marker in the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to assess the diagnostic and prognostic validity of a novel marker, serum Glypican‐3 (GPC3) and to compare AFP in patients with HCC. One hundred and twenty‐eight patients (75 patients with HCC, 55 patients with cirrhosis, and 28 healthy controls) were included in this study. Cut‐off value of GPC3 was 3.9 pg/ml. AFP was divided into four subgroups, according to cut‐off values with 13, 20, 100, and 200 ng/ml. Sensitivity, specificity, and positive and negative predictive values of GPC3 and AFP_13, AFP₂₀, AFP₁₀₀, AFP₂₀₀ subgroups and also GPC3+AFP_13, GPC3+AFP₂₀, GPC3+AFP₁₀₀, GPC3+AFP₂₀₀ combinations were compared. Serum GPC3 levels were significantly higher in patients with HCC and cirrhosis compared with control subjects (P<0.05). The median serum GPC3 levels were 3.9 pg/ml in controls, 5.51 pg/ml in patients with cirrhosis, and 5.13 pg/ml in those with HCC. The median serum AFP levels were 1.37 ng/ml in controls, 2.32 ng/ml in cirrhotics, and 50.65 ng/ml in HCC patients. The sensitivity, specificity, and positive and negative predictive values of GPC3 was 61.33, 41.82, 58.97, and 44.43%, respectively. The values for AFP were 68.57, 94.55, 94.12, and 70.27%, respectively. There was no correlation between GPC3 levels and prognostic parameters. GPC3 is not a useful diagnostic and prognostic marker for HCC. J. Clin. Lab. Anal. 25:350–353, 2011. © 2011 Wiley‐Liss, Inc.     

Functional glutathione peroxidase 3 polymorphisms associated with increased risk of Taiwanese patients with gastric cancer

BackgroundGlutathione peroxidase 3 (GPX3) can enhance an antioxidant's capacity and reduce genomic damage caused by oxidants and thus influence tumorigenesis. We investigated the role of GPX3 as a risk of gastric cancer.MethodsWe first conducted a case-control study to test for the association between 5 tagging single nucleotide polymorphisms (SNPs) of GPX3 and the risk of gastric cancer in Chinese. Multivariate logistic regression analysis was performed to estimate the genetic effect with adjustments for age and sex. Functional studies were performed by using the luciferase reporter assay to assess functional consequences of the significant SNPs.ResultsAmong five SNPs (rs3763013, rs8177412, rs3805435, rs3828599, and rs2070593) genotyped in 227 cases and 844 controls, 3 SNPs were significant: intronic SNP rs3805435 (OR = 0.70, P = 0.037), intronic SNP 3828599 (OR = 0.68, P = 0.025), and 3′ UTR SNP rs2070593 (OR = 0.48, P = 0.001). The two intronic SNPs rs3805435 and SNP rs3828599 were in linkage disequilibrium (D′ = 0.91).ConclusionsThe reporter assays showed significant difference in the luciferase expression between protective and risk alleles of 2o intronic SNPs (P = 0.004), whereas the 3′UTR SNP did not influence the luciferase expression. The intronic SNPs at GPX3 can influence gene expression leading to an alteration of gastric cancer risk.     

Association between genetic polymorphisms of the NPHS1 gene and membranous glomerulonephritis in the Taiwanese population

BackgroundMembranous glomerulonephritis (MGN) is one of the most common causes of nephrotic syndrome in adults. NPHS1 encoding nephrin is a transmembrane protein of the immunoglobulin family. We clarified the relationship between NPHS1 gene polymorphisms and the susceptibility or progression of MGN.MethodsWe recruited a cohort of 132 biopsy-diagnosed MGN patients and 257 healthy subjects. Genotyping of three SNPs (rs401824, rs437168 and rs3814995) at chromosome positions 41034749 (5′UTR), 41026259(exon17) and 41034052 (exon 3) was performed using a Taqman SNP genotyping assay.ResultsThere was a significant difference in genotype frequency distribution of rs437168 polymorphism between MGN patients and controls. The results also showed that the frequency of the G allele was significantly higher in the patient group. Among the polymorphisms rs437168, rs401824 and rs3814995, no significant haplotype was shown in MGN patients. A stratified analysis revealed that a high disease progression in the AA genotype of rs401824 and GG genotype of rs437168 patients were associated with a low rate of remission.ConclusionsThe presence of the different genotypes of NPHS1 was associated with susceptibility of MGN and the remission of proteinuria during disease progression after the therapy.     

Comparing the diagnostic value of serum oligosaccharide chain (G-test) and alpha-fetoprotein for hepatitis B virus-related liver cancer

ObjectivesThe study compared the diagnostic efficiency of serum oligosaccharide chain (G-test) and alpha-fetoprotein (AFP) for hepatitis B-related hepatocellular carcinoma (HCC).MethodsSerum samples from 100 patients (divided into five groups of 20 each, namely the hepatitis, liver cirrhosis, liver cancer, health, and interference groups) who were admitted to the Second Affiliated Hospital of Nanchang University from October 2019 to January 2020 were collected, and the levels of G-test and AFP were determined. The sensitivity and specificity of the two indicators were compared, and the receiver operating characteristic curve of the subjects was drawn to evaluate the diagnostic values of G-test and AFP for HCC.ResultsThe diagnostic ability of G-test (area under the curve [AUC]: 0.88 ± 0.05) was better than that of AFP (AUC: 0.76 ± 0.05). When G-test and AFP were combined for detection, the AUC was larger than that of either indicator. The G-test was superior to AFP in the differential diagnosis of early HCC and cirrhosis. A combination of the two indicators (AUC: 0.769 ± 0.05) significantly improved the diagnostic rate for early HCC, indicating that G-test and AFP complemented each other.ConclusionG-test was better than AFP for screening HCC in patients with chronic hepatitis B and cirrhosis. The combination of the two further improved the diagnostic rate of hepatitis B-related liver cancer. The G-test improves the screening rate of early HCC in patients with cirrhosis. Therefore, these markers are of great clinical significance and can improve the sensitivity of HCC detection and reduce missed diagnosis rates.     

Analysis of rs1864182 and rs1864183 variants in ATG10 gene and antineutrophil cytoplasmic autoantibody‐associated vasculitis in Chinese Guangxi population

ObjectivesTo investigate the association of autophagy‐associated gene 10 (ATG10) gene polymorphisms (rs1864182 and rs1864183) with antineutrophil cytoplasmic autoantibody (ANCA)‐associated vasculitis (AAV) in Chinese Guangxi population.MethodsThe single nucleotide polymorphisms (SNPs) of ATG10 rs1864182 and rs1864183 in 395 participants (195 AAVs and 200 healthy controls) were genotyped. Generalized multiple dimensionality reduction (GMDR) was used to analyze the SNP‐SNP interactions among two SNPs of ATG10 gene and other SNPs of autophagy gene previously studied by our research team.ResultsIn this study, we found that the two ATG10 SNPs were not associated with AAV risk in Chinese Guangxi population. However, there were statistically significant differences in the incidence of hemoptysis, hematuria, and proteinuria among the three genotypes of ATG10 rs1864182 and rs1864183 (p < 0.05). Moreover, permutation test of GMDR suggested that immunity‐related GTPase M(IRGM) rs4958847, autophagy‐associated gene 7 (ATG7) rs6442260, ATG7 rs2594966, ATG10 rs1864183, protein kinase B(AKT2) rs3730051, and AKT2 rs11552192 might interact with each other in the process of developing AAV (p < 0.05).ConclusionsOur results indicated that there existed no association between ATG10 SNPs and AAV, and SNP‐SNP interactions among IRGM rs4958847, ATG7 rs6442260, ATG7 rs2594966, ATG10 rs1864183, AKT2 rs3730051, and AKT2 rs11552192 may confer AAV risk in the Chinese Guangxi population.     

Replicated association between genetic variation in the PARK2 gene and blood pressure

BackgroundThe PARK2 gene encodes Parkin which is linked to the mitochondrial fusion, fission and mitophagy. In the previous study, single nucleotide polymorphisms (SNPs) in the PARK2 gene have been reported to be associated with blood pressure (BP) in Nigerian families. We aimed to confirm whether the genetic variation of the PARK2 gene influenced the susceptibility to BP and hypertension in Korean population.MethodsWe performed the quantitative BP trait analysis and hypertension case–control analysis for the 227 SNPs in the PARK2 gene in the Korean Association Resource (KARE) cohort (8512 subjects) and the Korean Urban Epidemiology (KUE) cohort (3703 subjects) by the independent association analysis and meta-analysis.ResultsTwo SNPs, rs9456721 and rs6902041, were significantly associated with systolic BP (SBP) and diastolic BP (DBP), respectively, in the KARE subjects, and their association p-values were below the Bonferroni-corrected significance level. The replication analysis in the KUE subjects revealed a significant association between the SNP, rs6902041 and BP.ConclusionsThese results indicate that genetic variation in the PARK2 gene is significantly associated with BP not only in the Nigerian population but also in the Korean population. This study may provide insight into the genetic basis of hypertension related to the mitochondrial quality control.     

A promoter polymorphism − 2122C>T of CHI3L1 is associated with serum low density lipoprotein cholesterol level in Korean subjects

ObjectivesThis study assessed the effects of 10 tagging single nucleotide polymorphisms (SNPs) of the CHI3L1 gene on serum LDL cholesterol levels in 290 Korean subjects.Design and methodsGenotyping analyses of SNPs were conducted by TaqMan® method. The effects of the promoter SNP on mRNA expression and nuclear factor binding were measured by real-time PCR and electrophoretic mobility shift assay, respectively.ResultsAmong 10 tagging SNPs, ? 2122C>T SNP (rs946261) in the promoter region was significantly associated with serum LDL cholesterol level (P = 0.005). The T allele of ? 2122C>T was associated with significantly increased mRNA expressions in peripheral blood cells of the subjects, and also increased a nuclear factor binding measured by an electrophoretic mobility shift assay.Conclusions? 2122C>T of CHI3L1, a promoter SNP which affects the mRNA expression and nuclear factor binding, is significantly associated with serum LDL cholesterol levels in Korean subjects.     

A polymorphism in the 3′-untranslated region of the matrix metallopeptidase 9 gene is associated with susceptibility to idiopathic calcium nephrolithiasis in the Chinese population

ObjectiveTo investigate whether single nucleotide polymorphisms (SNPs) in the 3′ untranslated region (UTR) of the matrix metallopeptidase 9 gene (MMP9) are associated with susceptibility to calcium oxalate stones.MethodsA total of 428 patients with kidney stone disease (KSD) and 450 control individuals were enrolled. Three MMP9 SNPs (rs20544, rs9509, and rs1056628) were genotyped, and MMP9 mRNA and protein expression was determined in patients and controls. The dual luciferase reporter gene assay was conducted by transfecting HEK293 cells with miR-491-5p mimics and plasmids containing MMP9 with rs1056628 AA/CC genotypes.ResultsThe rs1056628 CC genotype was significantly increased in KSD patients compared with controls (CC vs AA: odds ratio [OR] = 2.279, 95% confidence interval [CI] = 1.048–4.956). The rs1056628 C allele frequency was higher in KSD patients than controls. The increased KSD risks associated with rs1056628 were more evident in individuals aged <30 years (OR = 3.504, 95% CI = 1.102–11.139) and men (OR = 2.522, 95% CI = 1.004–6.334). mRNA and protein levels of MMP9 were significantly higher in KSD patients with the CC genotype than in those with the AA genotype.ConclusionThis study demonstrates that MMP9 SNP rs1056628 is associated with a significant KSD risk in Chinese Han individuals.     

Performance of SPINK1 and SPINK1‐based diagnostic model in detection of hepatocellular carcinoma

ObjectivesTo identify the SPINK1 or SPINK1‐based model as a more reliable biomarker for the diagnosis of hepatocellular carcinoma (HCC).MethodsSerum samples and related laboratory parameters were collected from 540 subjects (119 healthy donors, 113 patients with chronic hepatitis B, 122 patients with liver cirrhosis, and 186 patients with HCC). SPINK1 was determined by ELISA assay. Differences in each variable were compared by one‐way ANOVA or Kruskal‐Wallis test. ROC (receiver operating characteristic) curve analysis was conducted to compare the diagnostic efficiency of alpha‐fetoprotein (AFP), SPINK1, and a SPINK1‐based combine model constructed by binary Logistic regression.ResultsIn detecting HCC using the other three groups as control, ROC curve analysis revealed that SPINK1 alone reached AUC of 0.899 (0.866–0.933), with the sensitivity of 0.812 of and specificity of 0.953. The combined model increased the AUC to 0.945 (0.926–0.964) with the sensitivity and specificity of 0.860 and 0.910, respectively. For AFP, significantly lower AUC (p < 0.0001) was shown, which was 0.695 (0.645–0.745) with the sensitivity and specificity of 0.634 and 0.718, respectively. In discriminating HCC from liver disease control, AUC of SPINK1 was 0.863(0.826–0.894), the sensitivity and specificity were 0.823 and 0.906, respectively. For combined model, the AUC, sensitivity, and specificity were 0.915 (0.884–0.940), 0.863, and 0.916, respectively. For detecting early‐stage HCC, SPINK1 and combined model achieved the sensitivity of 0.788 and 0.818, respectively, much higher than AFP of 0.485 (p < 0.05); however, the difference between SPINK1 and combined model was not statistically significant (p = 1).ConclusionWe provided solid evidence for SPINK1 as a robust serological tool for HCC diagnosis.     

An SNP reducing SNORD105 and PPAN expression decreases the risk of hepatocellular carcinoma in a Chinese population

BackgroundWith hepatocellular carcinoma (HCC) becoming a heavy disease burden in China, it is particular to reveal its pathological mechanism. Recent researches have indicated that small nucleolar RNAs (snoRNAs) may be involved in various cancers including HCC. Polymorphisms within snoRNAs may affect its function or expression level, and even its host gene, then produce series of effects related to itself or its host gene.MethodsThe association of the single nucleotide polymorphism (SNP) rs2305789 in SNORD105 with HCC susceptibility was evaluated in two independent case‐control sets (712 HCC and 801 controls). The contribution of rs2305789 to HCC risk was investigated using case‐control, genotype‐phenotype correlation analysis, and functional assays.ResultsThe SNP rs2305789 was significantly associated with a decreased risk of HCC in both case‐control sets (OR = 0.80, 95% CI: 0.69–0.93, p = 0.003). Compared with the AA genotype, the GG genotype was significantly correlated with lower expression of both SNORD105 and PPAN (p < 0.01). Furthermore, the overexpressed SNORD105 up‐regulated PPAN expression level (p < 0.05). Finally, the in vivo experiment showed that the overexpressed SNORD105 increased cell viability and motility in both HepG2 and Huh7 cell lines (p < 0.05).ConclusionsTo sum up, our results suggested that rs2305789 decreased the risk of HCC by reducing the expression of both SNORD105 and PPAN, which reduced HCC cell viability and motility.     

Genetic variants in transient receptor potential cation channel, subfamily M 1 (TRPM1) and their risk of albuminuria-related traits in Mexican Americans

BackgroundEvidence for linkage of albuminuria to GABRB3 marker region on chromosome 15q12 was previously reported in Mexican Americans. The objective of this study is to scan a positional candidate gene, Transient Receptor Potential cation channel, subfamily M 1 (TRPM1), for genetic variants that may contribute to the variation in albumin-to-creatinine ratio (ACR).MethodsTo identify the sequence variants, the exons and 2 kb putative promoter region of TRPM1 were PCR amplified and sequenced in 32 selected individuals. Identified variants were genotyped in the entire data set (N = 670; 39 large families) by TaqMan assays. Association analyses between the sequence variants and ACR, type 2 diabetes (T2DM) and related phenotypes were carried out using a measured genotype approach as implemented in the program SOLAR.ResultsSequencing analysis identified 18 single nucleotide polymorphisms (SNPs) including 8 SNPs in the coding regions, 7 SNPs in the promoter region and 3 SNPs in introns. Of the 8 SNPs identified in the coding regions, 3 were non synonymous [Met(1)Thr, Ser(32)Asn, Val(1395)Ile] and one SNP caused stop codon (Glu1375/*). Of the SNPs examined, none of them exhibited statistically significant association with ACR after accounting for the effect of age, sex, diabetes, duration of diabetes, systolic blood pressure and anti-hypertensive medications. However, a SNP (rs11070811) located in the putative promoter region showed a modest association with triglycerides levels (P = 0.039).ConclusionThe present investigation found no evidence for an association between sequence variation at the TRPM1 gene and ACR in Mexican Americans, although it appears to have modest influence on T2DM risk factors.     

中国人群中单核苷酸多态性位点rs165599与脑区体积的相关性

目的 探讨健康中国汉族人群精神分裂症易感基因儿茶酚-O-甲基转移酶（COMT）单核苷酸多态性位点rs165599与部分脑区体积的相关性。方法 纳入299名健康中国汉族志愿者,对所有志愿者行MRI,采用VBM8软件测量19个脑区体积,以SnaP Shot法对rs165599位点进行基因分型,采用线性回归模型分析rs165599位点与所选19个脑区体积的相关性。结果 总体样本和男性样本中rs165599位点与所选19个脑区体积均无相关性（P均>0.05）;女性样本中rs165599位点与岛叶及丘脑体积呈显著相关（P=0.04、0.01）,效应等位基因（C）携带者岛叶体积大于非效应等位基因（T）携带者,丘脑体积小于非效应等位基因（T）携带者,经多重检验校正后rs165599与岛叶及丘脑体积无相关性（P=0.76、0.15）。结论 女性中rs165599可能与岛叶及丘脑体积具有相关性。     

Germline predictors of androgen deprivation therapy response in advanced prostate cancer

ObjectiveTo evaluate whether germline variations in genes involved in sex steroid biosynthesis and metabolic pathways predict time to treatment failure for patients with advanced prostate cancer undergoing androgen deprivation therapy (ADT), because there are few known clinical predictors of response.Patients and MethodsIn a cohort of 304 patients with advanced prostate cancer undergoing ADT, we genotyped 746 single-nucleotide polymorphisms (SNPs) from 72 genes from germline DNA (680 tagSNPs from 58 genes and 66 candidate SNPs from 20 genes [6 genes common in both]). Association with the primary end point of time to ADT failure was assessed using proportional hazards regression models at the gene level (for genes with tagging SNPs) and at the SNP level. False discovery rates (FDRs) of 0.10 or less were considered noteworthy to account for multiple testing.ResultsAt the gene level, TRMT11 showed the strongest association with time to ADT failure (P<.001; FDR=0.008). Two of 4 TRMT11 tagSNPs were associated with time to ADT failure. Median time to ADT failure for rs1268121 (A>G) was 3.05 years for the AA, 4.27 years for the AG, and 6.22 years for the GG genotypes (P=.002), and for rs6900796 (G>A), it was 2.42 years for the GG, 3.52 years for the AG, and 4.18 years for the AA genotypes (P<.001). No other gene level or SNP level tests had an FDR of 0.10 or less.ConclusionGenetic variation in TRMT11 was associated with time to ADT failure. Confirmation of these preliminary findings in an independent cohort is needed.     

Validation of the hepatocellular carcinoma early detection screening algorithm Doylestown and aMAP in a cohort of Chinese with cirrhosis

BackgroundPrevious studies have developed some blood‐based biomarker algorithms such as the Doylestown algorithm and aMAP score to improve the detection of Hepatocellular carcinoma (HCC). However, no one has studied the application of the Doylestown algorithm in the Chinese. Meanwhile, which of these two screening models is more suitable for people with liver cirrhosis remains to be investigated.MethodsIn this study, HCC surveillance was performed by radiographic imaging and testing for tumor markers every 6 months from August 21, 2018, to January 12, 2021. We conducted a retrospective study of 742 liver cirrhosis patients, and among them, 20 developed HCC during follow‐up. Samples from these patients at three follow‐up time points were tested to evaluate alpha‐fetoprotein (AFP), the Doylestown algorithm, and aMAP score.ResultsOverall, 521 liver cirrhosis patients underwent semiannual longitudinal follow‐up three times. Five patients were diagnosed with HCC within 0–6 months of the third follow‐up. We found that for these liver cirrhosis patients, the Doylestown algorithm had the highest accuracy for HCC detection, with areas under the receiver operating characteristic curve (AUCs) of 0.763, 0.801, and 0.867 for follow‐ups 1–3, respectively. Compared with AFP at 20 ng/ml, the Doylestown algorithm increased biomarker performance by 7.4%, 21%, and 13% for follow‐ups 1–3, respectively.ConclusionsOur findings show that the Doylestown algorithm performance appeared to be optimal for HCC early screening in the Chinese cirrhotic population when compared with the aMAP score and AFP at 20 ng/ml.     

Inter-alpha-trypsin inhibitor heavy chain H4 as a diagnostic and prognostic indicator in patients with hepatitis B virus-associated hepatocellular carcinoma

ObjectivesInter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) is associated with various diseases. We evaluated the diagnostic and prognostic significance of serum ITIH4 levels in healthy controls and patients with chronic hepatitis B (CHB), hepatitis B virus (HBV)-related liver cirrhosis, and HBV-related hepatocellular carcinoma (HCC).Design and methodsThe study enrolled 300 individuals (50 healthy controls, 50 with CHB, 100 with HBV-associated cirrhosis, and 100 with HBV-associated HCC). Serum ITIH4 levels were determined by western blot analysis and expressed in densitometry units (DU).ResultsITIH4 levels were higher in CHB (mean: 252.96 DU) and liver cirrhosis (mean: 206.43 DU) patients than in healthy controls (mean: 75.92 DU) and HCC patients (mean: 92.86 DU) (P < 0.001). The area under the receiver operating characteristic curve was 0.71 for the diagnosis of HCC in patients with HBV-related liver disease. Multivariate Cox regression analysis showed that large tumor size (≥ 5 cm) was independently associated with overall survival (hazard ratio 5.894, 95% confidence interval 1.373–25.300, P = 0.017). A Kaplan–Meier survival analysis showed significantly worse survival among HCC patients with both low ITIH4 (< 80 DU) and a large tumor size compared to that among other HCC patients (P < 0.001), and among patients with high AFP (> 200 ng/mL) and low ITIH4 compared to that among other HCC patients (P = 0.041).ConclusionsSerum ITIH4 levels are reduced in HCC patients compared to that in CHB and cirrhosis patients, and low serum ITIH4 levels are associated with shorter survival in HBV-associated HCC patients.     

Meta-analysis reveals significant association between FOXP3 polymorphisms and susceptibility to Graves’ disease

ObjectiveThis meta-analysis aimed to determine the associations between the rs3761547, rs3761548, and rs3761549 single-nucleotide polymorphisms (SNPs) of the forkhead box P3 (FOXP3) gene and susceptibility to Graves’ disease (GD).MethodsCase–control studies with information on the associations between the rs3761547, rs3761548, and rs3761549 FOXP3 SNPs and GD published before 01 May 2020 were identified in the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases. Data from the studies were analyzed using RevMan version 5.3.ResultsSeven independent case–control studies including 4051 GD patients and 4569 controls were included in the meta-analysis. The overall pooled analysis indicated that FOXP3/rs3761548 and FOXP3/rs3761549 polymorphisms were significantly associated with GD susceptibility (rs3761548: A vs. C, odds ratio [OR] = 1.32, 95% confidence interval [CI] 1.05–1.67; rs3761549: TT vs. CC, OR = 1.98, 95%CI 1.49–2.65; (TT + TC) vs. CC, OR = 1.44, 95%CI 1.11–1.88). In contrast, the FOXP3/rs3761547 polymorphism was not associated with GD susceptibility. Subgroup analysis according to ethnicity showed that rs3761548 was associated with GD in Asians but not in Caucasians, whereas rs3761549 was associated in both Asians and Caucasians.ConclusionThis meta-analysis demonstrated that FOXP3/rs3761548 and FOXP3/rs3761549 SNPs were significantly associated with susceptibility to GD, at least in Asian populations.     

Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese

ObjectivesGenome-wide association studies (GWAS) and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and FAM13A polymorphisms in non-Asian populations. The aim of this study was to investigate whether FAM13A polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population.MethodsSeven single nucleotide polymorphisms (SNPs) (rs7671167, rs10007590, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) in FAM13A gene were genotyped in a case–control study (680 COPD patients and 687 controls). 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.ResultsStatistical analysis revealed that SNP rs7671167 was associated with COPD in former smokers with adjusted P-value of 0.026. Five SNPs (rs7671167, rs2869966, rs2869967, rs2045517, and rs6830970) were associated with FEV1/FVC ratio in the entire cohort and rs6830970 was associated with FEV1/FVC ratio in COPD cases (P range 0.003–0.034). Borderline associations with FEV1/FVC ratio were found for rs2869966, rs2869967 and rs2045517 among cases (P = 0.05). Six SNPs (rs7671167, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) showed strong linkage disequilibrium (r² ≥ 0.9). Four major haplotypes were observed but showed no significant difference between case and control groups (P = 0.2356, 0.1273, 0.6266 and 0.3006 respectively).ConclusionsThe current study suggests that the FAM13A locus might be a contributor to COPD susceptibility in Chinese Han population.     

Effect of obesity on the association between common variations in the HNF1A gene region and C-reactive protein level in Taiwanese

BackgroundThe level of C-reactive protein (CRP), an inflammatory biomarker that predicts future cardiovascular events, is a heritable trait that has been associated with variants of CRP and hepatic nuclear factor-1α (HNF1A) genes. Our aim was to test the statistical association between HNF1A genotypes/haplotypes and serum CRP level in Taiwanese.MethodsA sample population of 617 Taiwanese subjects (all Han-Chinese origin) was enrolled. Five HNF1A single nucleotide polymorphisms (SNPs) rs1920792, rs1169288, rs7310409, rs2464196, rs1169310 were genotyped and analyzed.ResultsAfter adjusting for clinical covariates, minor alleles of all the 5 study SNPs were associated with decreased CRP level (P = 0.0078, P = 0.0107, P = 0.0006, P = 0.0004 and P = 0.0003, respectively). A common haplotype (TGATA) tagged by the minor alleles of study SNPs was associated with significantly decreased CRP level (P = 0.0112). Subgroup analysis revealed that the association between HNF1A genotypes and CRP level occurred only in non-obese subjects.ConclusionsHNF1A polymorphisms are independently associated with CRP level in Taiwanese. Further, HNF1A genotypes interact with obesity to set CRP level, revealing that genetic determinants for CRP level may be different between obese and non-obese individuals.