广西百色地区壮族妇女脂联素基因单核苷酸多态性与骨密度的关系

目的 探讨脂联素(APN)基因5个单核苷酸多态性(SNPs)与广西百色地区壮族妇女骨矿物质密度(BMD)的关系.方法 选取壮族女性239例跟骨骨量减少患者(LBM)和83例正常骨量组(NBM)进行病例对照研究,采用多重单碱基延伸SNP分型技术对壮族女性脂联素基因的5个位点(rs1063539、rs12495941、rs266729 、rs3774261 及rs710445)进行了基因分型,采用法国生产的Osteospace干式超声骨密度仪测量右侧跟骨超声振幅衰减(BUA).结果 仅rs1063539、rs12495941、rs266729及rs710445多态性分布符合Hardy-Weinberg遗传平衡定律(P>0.05).除rs3774261在骨量正常组的分布不符合Hardy-Weinberg平衡(P<0.05)之外,其余位点在正常组和骨量减少组基因型分布均符合Hardy-Weinberg平衡(P>0.05).其中,只有rs1063539 基因型在NOR和LBM组差异存在显著性(P=0.003),CG基因型者在LBM组人数明显多于GG型(P<0.01).调整年龄、体重、身高及体质指数后,以5个多态性位点作为自变量的多元 Logistic回归显示,仅rs1063539多态性与跟骨BUA相关性有统计学意义(adjusted OR=3.210,95%CI:1.631～6.137,P=0.001),并独立于骨量减少的传统危险因素.结论 APN基因第3外显子rs1063539多态性与壮族女性 BMD有一定关联,其中GG型对BMD具有一定的保护作用,CG型是BMD降低的危险因素.rs12495941、rs266729、rs3774261及rs710445多态性与壮族女性BMD无相关性.     

Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity

Adiponectin is an insulin sensitiser in muscle and liver, and low serum levels characterise obesity and insulin resistance. Eight tagging single nucleotide polymorphisms (tSNPs) in the ADIPOQ gene and promoter were selected, and association with serum adiponectin was tested, in two independent samples of Caucasian women: the Chingford Study (n = 808, mean age 62.8 +/- 5.9 years) and Twins UK (n = 2,718, mean age 47.4 +/- 12.6 years). In the Chingford cohort, -11391 G/A, -10066 G/A (rs182052), -7734 C/A (rs16861209), +276 G/T (rs1501299) and +3228 C/T (rs1063537) were significantly associated with fasting serum adiponectin (Ps = 1.00 x 10(-4) to 1.40 x 10(-2)). Associations with all except +3228 C/T were replicated in the Twins UK cohort (Ps = 3.19 x 10(-9) to 6.00 x 10(-3)). In Chingford subjects, the 12 most common 8-SNP haplotypes (frequency 1.90%) explained 2.85% (p = 5.00 x 10(-2)) and in Twins UK subjects, the four most common 5-SNP haplotypes (frequency > 5.00%) explained 1.66% of the variance (p = 5.83 x 10(-7)). To investigate effects of -11391 G/A (rs17300539) and -11377 C/G (rs266729) on promoter activity, 1.2 kb of the ADIPOQ promoter region was cloned in a luciferase reporter plasmid, and the four haplotypes were transfected in differentiated 3T3-L1 adipocytes. No significant allelic effects on promoter activity were found.     

广西百色地区壮族男性人群骨密度与脂联素基因单核苷酸多态性的关系

背景：脂联素可在骨代谢中发挥重要作用。 目的：观察脂联素基因单核苷酸多态性与广西百色地区壮族男性骨密度的关系。 方法：选取广西百色地区壮族男性跟骨骨量减少患者,采用单碱基延伸的单核苷酸多态性分型技术对广西百色地区302例壮族男性的脂联素基因的5个单核苷酸多态性位点(rs1063539、rs12495941、rs266729和rs3774261)进行了基因分型。 结果与结论：以5个多态性位点作为自变量的多元 Logistic回归检测结果显示,仅rs3774261多态性与跟骨超声振幅衰减显著相关(OR=1.948,95%CI：1.184~3.203,P < 0.01),并独立于骨量减少的传统危险因素。对基因型进行纯合子与杂合子合并后的协方差分析显示,仅rs3774261的AG+GG与AA基因型的跟骨超声振幅衰减值差异有显著性意义(P < 0.05),AG+GG型对骨密度具有一定的保护作用,AA型是骨密度降低的危险因素。结果证实,脂联素基因第2内含子rs3774261位点多态性与中国百色地区壮族男性骨密度有一定关联。     

Association between the three functional miR-146a single-nucleotide polymorphisms,rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164?G?>?C was found to be associated with increased risk of multiple sclerosis (CC?+?CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC?+?GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC?+?GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC?+?GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC?+?CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C?>?T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC?+?TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC?+?CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A?>?G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.     

CDH13 gene coding T-cadherin influences variations in plasma adiponectin levels in the Japanese population

Adiponectin is most abundantly expressed in adipose tissue and well known to play an important role in metabolic regulation. Several studies have attempted to identify the genetic determinants of metabolic syndrome (MetS), though no study has revealed a cis- or trans-single nucleotide polymorphism (SNP) that affects plasma adiponectin levels, except the adiponectin structure gene and genes encoding adiponectin-regulatory proteins. We performed a genome-wide association study in regards to plasma adiponectin concentrations in 3,310 Japanese subjects. We identified the strongest statistically associated SNP (rs4783244) with adiponectin levels (P = 3.8 × 10(-19)) in the first intron of CDH13 (T-cadherin) gene in a 30-kb haplotype block covering the promoter region to first intron. In addition, rs12051272 SNP genotypes in linkage disequilibrium with rs4783244 were found to be more significantly associated with adiponectin levels (P = 9.5×10(-20)) and specifically with the levels of high-molecular weight (HMW) adiponectin, a subtype form associated with parameters related to glucose metabolism. Our results did show more significant association with adiponectin levels than rs12444338 (in CDH13) SNP genotypes reported recently. We suggest that the phenotype-affecting haplotype tagged by rs12051272 SNP would affect the plasma adiponectin levels and that we have to take the CDH13 genotype into account before considering the functional relevance of the adiponectin level.     

Genetic variants in the ADIPOQ gene and the risk of metabolic syndrome: a case-control study of a Chinese Han population

Our aim was to investigate whether the ADIPOQ gene polymorphisms are associated with the metabolic syndrome (MetS). Genotypes of MetS patients (n= 1049) and normal controls (n= 1092) were analysed by TaqMan® assay, and serum adiponectin concentration was measured by ELISA. The variant genotypes rs266729CG; rs1063539GC, GC/CC; rs16861205AA and rs7649121AT, AT/TT (Adjusted P= 0.037, 0.044, 0.025, 0.011, 0.019, 0.020, respectively) of the ADIPOQ gene were associated with MetS. Patients with rs266729CG, CG/GG genotypes (P= 0.034, 0.035) and rs7649121AT, AT/TT genotypes (P= 0.013, 0.022) had higher levels of serum adiponectin than those with the CC and AA genotypes respectively. Furthermore, the prevalence of haplotypes GGAAAATC and GGGTAACC was lower in cases (10.7% and 4.5%) than in controls (12.1% and 5.9%) [Adjusted ORs (95% CIs) = 0.70 (0.54–0.91), 0.65 (0.46–0.92)]. The ADIPOQ gene variants associated with the risk of MetS in this study must be validated by further functional studies to reveal any potential effects on metabolism.     

Population-specific coding variant underlies genome-wide association with adiponectin level

Adiponectin is a protein hormone that can affect major metabolic processes including glucose regulation and fat metabolism. Our previous genome-wide association (GWA) study of circulating plasma adiponectin levels in Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS) detected a 100 kb two-SNP haplotype at KNG1-ADIPOQ associated with reduced adiponectin (frequency = 0.050, P = 1.8 × 10(-25)). Subsequent genotyping of CLHNS young adult offspring detected an uncommon variant [minor allele frequency (MAF) = 0.025] located ~800 kb from ADIPOQ that showed strong association with lower adiponectin levels (P = 2.7 × 10(-15), n = 1695) and tagged a subset of KNG1-ADIPOQ haplotype carriers with even lower adiponectin levels. Sequencing of the ADIPOQ-coding region detected variant R221S (MAF = 0.015, P = 2.9 × 10(-69)), which explained 17.1% of the variance in adiponectin levels and largely accounted for the initial GWA signal in Filipinos. R221S was not present in 12 514 Europeans with previously sequenced exons. To explore the mechanism of this substitution, we re-measured adiponectin level in 20 R221S offspring carriers and 20 non-carriers using two alternative antibodies and determined that the presence of R221S resulted in artificially low quantification of adiponectin level using the original immunoassay. These data provide an example of an uncommon variant responsible for a GWA signal and demonstrate that genetic associations with phenotypes measured by antibody-based quantification methods can be affected by uncommon coding SNPs residing in the antibody target region.     

Associations of single nucleotide polymorphisms in the adiponectin gene with adiponectin levels and cardio-metabolic risk factors in patients with cancer

Objectives: The aims of this study are to (1) study the influence of polymorphisms in adiponectin gene on adiponectin levels and potential associations with breast, prostate and colon cancer; (2) investigate the associations of adiponectin levels with other adipokines and breast, prostate and colon cancers. Subjects: We measured fasting adiponectin, leptin, insulin, Sex steroids in 132 (66 females, 66 males) cancer patients and 68 age and sex matched apparently healthy subjects. Body Mass Index (BMI) and waist circumference were used as indices of obesity. Insulin Resistance was assessed using Homeostasis Model Assessment (HOMA). Three single nucleotide polymorphisms (SNP rs182052 (G-10066-A), SNP rs1501299 (276G > T), SNP rs224176 (45T > G) in adiponectin gene were studied using Real Time Polymerase Chain Reaction. Results: GG genotype of SNP rs1501299 was significantly associated with higher levels of adiponectin (OR=1.2, 95%CI(1.03–1.3), p = 0.02); breast (OR=8.6, 95%CI(1.03–71), p = 0.04), colon cancers (OR= 12, 95%CI(1.2–115), p = 0.03). GT genotype was also associated significantly with colon cancer (OR=2.6, 95%CI (1.1–6), p = 0.03). However SNP rs224176 was associated with only breast cancer. Conclusion: Our results demonstrate that adiponectin gene SNP rs1501299 and SNP rs224176 may be the predisposing factors in some cancers but our results differ from what has been reported in other populations suggesting a complex relationship between genetic variations and phenotypic adiponectin levels.     

小于胎龄儿脐血脂联素水平测定及其临床意义

目的探讨小于胎龄儿（SGA）脐血脂联素（APN）水平变化及其对新生儿的影响。方法研究对象为SGA和适于胎龄儿（AGA）各30例。采用放射免疫分析法测定脐血和产妇血脂联素水平。用免疫比浊法测定三酰甘油（TG）,总胆固醇（TCH）,低密度脂蛋白胆固醇（LDL-C）,高密度脂蛋白胆固醇（HDL-c）水平。并分析脐血脂联素水平与母血脂联素,体质量指数（IBM）,胎盘重量和血脂水平的相关性。结果1.SGA脐血脂联素水平低于AGA差异有显著性（P〈0.01）;SGA血TG,TCH,LDL-c,HDL-c水平与AGA比较差异均无显著性（P〉0.05）。2.SGA血清脂联素水平与新生儿身长,新生儿体质量指数BMI,胎盘重量,脐血TG呈显著正相关（r=0.386,0.431,0.365,0.231,P〈0.05）,与母血脂联素水平,孕前和分娩时产妇IBM无相关性（P〉0.05）。结论小于胎龄儿具有较低血清脂联素水平,测定脐血脂联素水平有助于判断SGA的发展趋势。     

Relation of a common variant of the adiponectin gene to serum adiponectin concentration and metabolic traits in an aged Japanese population

Adiponectin is an adipocyte-derived protein that is down-regulated in obesity-linked disorders. Variants of the adiponectin gene (ADIPOQ) have been shown to affect adiponectin level. We have now examined the relation of polymorphisms of ADIPOQ to adiponectin concentration and to metabolic disorders in the Kita-Nagoya Genomic Epidemiology study, a population-based study of elderly Japanese. The genomic region including ADIPOQ was genotyped for 30 single nucleotide polymorphisms in 500 subjects of a screening population with the use of a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Four polymorphisms were then selected for genotyping in an additional 2797 subjects. Serum adiponectin level was negatively associated with metabolic abnormalities after adjustment for age and sex. The minor alleles of the rs1656930, Ile164Thr, and rs9882205 polymorphisms were associated with a low serum adiponectin level. Whereas the minor alleles of rs1656930 and rs9882205 were common (minor allele frequency of 6.2 and 38.5%, respectively), that of Ile164Thr was rare (0.9%). The minor allele of rs1656930 was positively associated with systolic blood pressure and the prevalence of hypertension. The association of rs1656930 with adiponectin level was replicated in an independent population. A subject with the 164Thr/Thr genotype had an extremely low serum adiponectin level (0.6 μg/ml) and the phenotype of metabolic syndrome. Our results suggest that a common variant of ADIPOQ, the minor allele of rs1656930, is associated with hypoadiponectinemia and hypertension. Screening for a common genetic background underlying low adiponectin levels might provide important information for assessment and management of metabolic disorders.     

A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries

Keratoconus is a condition in which the cornea progressively thins over time, and is a major cause for cornea transplantation. To identify keratoconus susceptibility regions, we performed a comprehensive genome-wide association study (GWAS) using a discovery and replication design. A discovery panel of 222 keratoconus Caucasian patients and 3324 Caucasian controls was genotyped using Illumina 370K beadchips. Further associated and fine-mapping single nucleotide polymorphisms (SNPs) (n= 4905) were genotyped in an independent replication case-control panel of 304 cases and 518 controls and a family panel of 307 subjects in 70 families. Logistic regression models implemented in PLINK were performed to test associations in case-control samples with and without principal component (PC) adjustments. Generalized estimation equation models accounting for familial correlations implemented in GWAF were used for association testing in families. No genome-wide associations were identified in the discovery GWAS panel. From the initial testing without adjustments for PCs, the top three SNPs located at 3p26 (rs6442925), 2q21.3 (rs4954218) and 19q13.3 (rs1428642) were identified with unadjusted P-values of 6.5 × 10(-8), 2.4 × 10(-7) and 3.1 × 10(-7), respectively. After adjustments for PCs, rs1428642 became the most significant through the genome with a P-value of 1.4 × 10(-6), while rs6442925 and rs4954218 were less significant (P= 1.9 × 10(-5) and 2.6 × 10(-4)). SNP rs4954218 was confirmed in two independent replication panels with P-values of 0.004 and 0.009, respectively. Meta-analysis revealed a highest association at rs4954218 with adjusted P= 1.6 × 10(-7) (unadjusted P= 1.2 × 10(-9)). These findings suggest SNP rs4954218, located near the RAB3GAP1 gene, previously reported to be associated with corneal malformation, is a potential susceptibility locus for keratoconus.     

Gene polymorphisms related to insulin resistance and gene–environment interaction in colorectal cancer risk

Background and aim: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC) and both IR and CRC physiologically overlap. As such, this study explored the relationship of IR-related gene polymorphisms and CRC risk.

Subjects and methods: A total of 400 case-control pairs were profiled in terms of their lifestyle, dietary habits and blood sample. Classification and regression tree (CART) and generalized multi-factor dimensionality reduction (GMDR) were employed to test the gene–environment interactions in CRC risk.

Results: ADIPOQ rs2241766 TG?+?GG, ADIPOQ rs1501299 GT?+?TT and CAPN-10 rs3792267 GA?+?AA were significantly related to CRC risk. In CART, individuals with high red meat consumption, CAPN-10 rs3792267 GG, ADIPOQ rs1501299 GG and ADIPOQ rs2241766 TG?+?GG had an OR of 1.821 (95% CI?=?1.124–2.951). The overall best GMDR model including the four factors had the maximal TBA (0.5943) and CVC (10/10) (p?=?0.0010). Subjects with high red meat consumption and the three risk genotypes had a CRC risk 10.195-times (95% CI?=?2.164–48.030) greater than those with low red meat and null risk genotypes.

Conclusions: ADIPOQ rs2241766, ADIPOQ rs1501299 and CAPN-10 rs3792267 are significantly associated with CRC risk and the combination of the three polymorphisms and red meat affect CRC risk.     

Cord blood resistin and adiponectin in term newborns of diabetic mothers

Introduction

Adipose tissue can release hormones into the blood stream in response to specific extracellular stimuli or changes in metabolic status. Resistin, an adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. Adiponectin, an adipocyte-specific hormone with insulin sensitizing, anti-inflammatory and anti-atherogenic effects, is reduced in obesity and type II diabetes. The aim of the study was to assess the influence of maternal pre-existing diabetes on cord blood resistin and adiponectin at birth in relation to neonatal anthropometric parameters and cord blood insulin levels.

Material and methods

A total of 60 term newborns were prospectively enrolled and categorized into three groups: 20 were macrosomic infants of pre-gestational diabetic mothers (group I), 20 were non-macrosomic infants of pre-gestational diabetic mothers (group II) and 20 were healthy non-macrosomic infants born to non-diabetic mothers serving as controls (group III). Infants’ anthropometric indices were recorded. Cord blood samples for glucose, insulin, resistin and adiponectin assay, together with maternal glycosylated haemoglobin were obtained.

Results

Serum insulin was increased while resistin and adiponectin were significantly decreased in infants of diabetic mothers (IDMs) compared to the control group. Serum glucose, insulin, resistin and adiponectin were comparable in group I and II. Cord serum resistin correlated positively with cord blood glucose in IDMs in both macrosomic and non-macrosomic groups. Cord serum insulin correlated positively with triceps skinfold thickness in all studied neonates. Cord serum resistin and adiponectin showed no correlation with neonatal anthropometric indices. Multiple regression analysis demonstrated that insulin, resistin and adiponectin together were highly correlated with birth weight, with adiponectin as the one responsible for this positive correlation.

Conclusions

Infants of diabetic mothers had elevated levels of cord serum insulin and suppressed levels of cord serum resistin and adiponectin, suggesting that the regulation of these metabolic pathways is probably operational before birth. Levels were comparable in both macrosomic and non-macrosomic neonates.     

STAT3 and STAT5b polymorphism contributes to breast cancer risk and clinical outcomes

We conducted a case-control study in a Chinese population, and investigated the role of STAT3 rs4796793 and STAT5b rs6503691 polymorphisms in the risk and clinical outcome of breast cancer. STAT5b rs6503691 polymorphisms and STAT3 rs4796793 polymorphisms were genotyped by TaqMan SNP Genotyping Assays on the ABI 7500 fast real-time PCR platform. Unconditional logistic regression analyses showed that subjects carrying the GG genotype of STAT3 rs4796793 had a significantly increased risk of breast cancer, with an adjusted OR (95% CI) of 0.35 (0.12-0.95). In the Cox proportional hazards model, we observed that individuals carrying CG+GG genotype of STAT3 rs4796793 was associated with reduced risk of death from breast cancer when compared with CC genotype (HR = 0.43, 95% CI = 0.20-0.93). Our study found that STAT3 rs4796793 polymorphism plays an important role in influence the development and overall survival of breast cancer patients.     

妊娠期糖尿病组脐血脂联素的变化及意义

目的观察妊娠期糖尿病脐血脂联素水平的变化,分析其与新生儿出生体重、劳雷尔指数及胰岛素抵抗之间的关系。方法应用酶联免疫吸附法及放射免疫分析法分别测定30例正常妊娠及26例妊娠期糖尿病新生儿脐血血清脂联素及胰岛素水平,同时测定空腹血糖、新生儿体重及身高,计算HOMA-IR指数及劳雷尔指数。结果 （1）妊娠期糖尿病组新生儿脐血脂联素水平低于正常对照组（P〈0.05）;（2）脐血脂联素水平与新生儿出生体重、劳雷尔指数及HOMA-IR呈显著负相关。结论妊娠期糖尿病组新生儿脐血脂联素水平明显下降,并与体脂含量及胰岛素抵抗相关,提示脂联素可能参与了胎儿的宫内发育过程。     

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.     

Meta-Analysis of Adiponectin Polymorphisms and Colorectal Cancer Risk

Objective The adiponectin gene (ADIPOQ) has been suggested to be associated with the pathogenesis of colorectal cancer (CRC). However, the results have been inconsistent. In this study, we performed a meta-analysis to investigate the association between adiponectin polymorphisms and CRC risk.Methods All eligible case-control studies published up to March 2013 were identified by searching PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model.Results A total of 9 case-control studies were included, Of those studies, there were eight studies (2024 cases and 2777 controls) for rs1501299G/T polymorphism, five studies (1401 cases and 1691 controls) for rs2241766T/G polymorphism, five studies (2945 cases and 3361 controls) for rs266729C/G polymorphism, three studies (1221 cases and 1579 controls) for rs822395A/C polymorphism and three studies (1222 cases and 1575 controls) for rs822396A/G polymorphism. Overall, a significant association was observed for rs2241766T/G polymorphism under heterozygote comparison (TG vs. TT: OR=1.22, 95%CI: 1.05-1.43); while there was no significant association for rs2241766 polymorphism under other genetic models, and for other four polymorphisms under all genetic models. Besides, when stratified analyses by ethnicity, no significant association between five polymorphisms and CRC risk were observed under all genetic models among Asian, Caucasian and African-American.Conclusions This meta-analysis indicated that adiponectin rs2241766T/G rather than rs1501299G/T, rs266729C/G, rs822395A/C and rs822396A/G polymorphism was associated with the risk of colorectal cancer.     

Fine mapping the TAGAP risk locus in rheumatoid arthritis

A common allele at the TAGAP gene locus demonstrates a suggestive, but not conclusive association with risk of rheumatoid arthritis (RA). To fine map the locus, we conducted comprehensive imputation of CEU HapMap single-nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) of 5,500 RA cases and 22,621 controls (all of European ancestry). After controlling for population stratification with principal components analysis, the strongest signal of association was to an imputed SNP, rs212389 (P=3.9 × 10(-8), odds ratio=0.87). This SNP remained highly significant upon conditioning on the previous RA risk variant (rs394581, P=2.2 × 10(-5)) or on a SNP previously associated with celiac disease and type I diabetes (rs1738074, P=1.7 × 10(-4)). Our study has refined the TAGAP signal of association to a single haplotype in RA, and in doing so provides conclusive statistical evidence that the TAGAP locus is associated with RA risk. Our study also underscores the utility of comprehensive imputation in large GWAS data sets to fine map disease risk alleles.