Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 15

Publication Record

Connections

Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression.
Darabi H, McCue K, Beesley J, Michailidou K, Nord S, Kar S, Humphreys K, Thompson D, Ghoussaini M, Bolla MK, Dennis J, Wang Q, Canisius S, Scott CG, Apicella C, Hopper JL, Southey MC, Stone J, Broeks A, Schmidt MK, Scott RJ, Lophatananon A, Muir K, Beckmann MW, Ekici AB, Fasching PA, Heusinger K, Dos-Santos-Silva I, Peto J, Tomlinson I, Sawyer EJ, Burwinkel B, Marme F, Guénel P, Truong T, Bojesen SE, Flyger H, Benitez J, González-Neira A, Anton-Culver H, Neuhausen SL, Arndt V, Brenner H, Engel C, Meindl A, Schmutzler RK, German Consortium of Hereditary Breast and Ovarian Cancer, Arnold N, Brauch H, Hamann U, Chang-Claude J, Khan S, Nevanlinna H, Ito H, Matsuo K, Bogdanova NV, Dörk T, Lindblom A, Margolin S, kConFab/AOCS Investigators, Kosma VM, Mannermaa A, Tseng CC, Wu AH, Floris G, Lambrechts D, Rudolph A, Peterlongo P, Radice P, Couch FJ, Vachon C, Giles GG, McLean C, Milne RL, Dugué PA, Haiman CA, Maskarinec G, Woolcott C, Henderson BE, Goldberg MS, Simard J, Teo SH, Mariapun S, Helland Å, Haakensen V, Zheng W, Beeghly-Fadiel A, Tamimi R, Jukkola-Vuorinen A, Winqvist R, Andrulis IL, Knight JA, Devilee P, Tollenaar RA, Figueroa J, García-Closas M, Czene K, Hooning MJ, Tilanus-Linthorst M, Li J, Gao YT, Shu XO, Cox A, Cross SS, Luben R, Khaw KT, Choi JY, Kang D, Hartman M, Lim WY, Kabisch M, Torres D, Jakubowska A, Lubinski J, McKay J, Sangrajrang S, Toland AE, Yannoukakos D, Shen CY, Yu JC, Ziogas A, Schoemaker MJ, Swerdlow A, Borresen-Dale AL, Kristensen V, French JD, Edwards SL, Dunning AM, Easton DF, Hall P, Chenevix-Trench G
(2015) Am J Hum Genet 97: 22-34
MeSH Terms: Age Factors, Asian Continental Ancestry Group, Autophagy-Related Proteins, Body Mass Index, Breast Neoplasms, Chromosome Mapping, Chromosomes, Human, Pair 10, DNA-Binding Proteins, Enhancer Elements, Genetic, European Continental Ancestry Group, Female, Gene Expression Regulation, Genome-Wide Association Study, Genotype, Humans, Luciferases, Odds Ratio, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Regression Analysis, Trans-Activators, Transcription Factors
Show Abstract · Added February 22, 2016
Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.
Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
22 MeSH Terms
Parkinson disease loci in the mid-western Amish.
Davis MF, Cummings AC, D'Aoust LN, Jiang L, Velez Edwards DR, Laux R, Reinhart-Mercer L, Fuzzell D, Scott WK, Pericak-Vance MA, Lee SL, Haines JL
(2013) Hum Genet 132: 1213-21
MeSH Terms: Amish, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Computational Biology, Genetic Linkage, Genetic Loci, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Indiana, Ohio, Parkinson Disease, Pedigree, Polymorphism, Single Nucleotide
Show Abstract · Added February 22, 2016
Previous evidence has shown that Parkinson disease (PD) has a heritable component, but only a small proportion of the total genetic contribution to PD has been identified. Genetic heterogeneity complicates the verification of proposed PD genes and the identification of new PD susceptibility genes. Our approach to overcome the problem of heterogeneity is to study a population isolate, the mid-western Amish communities of Indiana and Ohio. We performed genome-wide association and linkage analyses on 798 individuals (31 with PD), who are part of a 4,998 member pedigree. Through these analyses, we identified a region on chromosome 5q31.3 that shows evidence of association (p value < 1 × 10(-4)) and linkage (multipoint HLOD = 3.77). We also found further evidence of linkage on chromosomes 6 and 10 (multipoint HLOD 4.02 and 4.35 respectively). These data suggest that locus heterogeneity, even within the Amish, may be more extensive than previously appreciated.
0 Communities
1 Members
0 Resources
17 MeSH Terms
New breast cancer risk variant discovered at 10q25 in East Asian women.
Shi J, Sung H, Zhang B, Lu W, Choi JY, Xiang YB, Kim MK, Iwasaki M, Long J, Ji BT, Park SK, Zheng Y, Tsugane S, Yoo KY, Wang W, Noh DY, Han W, Kim SW, Lee MH, Lee JW, Lee JY, Shen CY, Matsuo K, Ahn SH, Gao YT, Shu XO, Cai Q, Kang D, Zheng W
(2013) Cancer Epidemiol Biomarkers Prev 22: 1297-303
MeSH Terms: Adult, Asian Continental Ancestry Group, Breast Neoplasms, China, Chromosome Mapping, Chromosomes, Human, Pair 10, Female, Genetic Loci, Genetic Predisposition to Disease, Genotype, Humans, Japan, Middle Aged, Polymorphism, Single Nucleotide, Republic of Korea, Risk Factors
Show Abstract · Added December 10, 2013
BACKGROUND - Recently, 41 new genetic susceptibility loci for breast cancer risk were identified in a genome-wide association study (GWAS) conducted in European descendants. Most of these risk variants have not been directly replicated in Asian populations.
METHODS - We evaluated nine of those nonreplication loci in East Asians to identify new risk variants for breast cancer in these regions. First, we analyzed single-nucleotide polymorphisms (SNP) in these regions using data from two GWAS conducted among Chinese and Korean women, including 5,083 cases and 4,376 controls (stage 1). In each region, we selected an SNP showing the strongest association with breast cancer risk for replication in an independent set of 7,294 cases and 9,404 controls of East Asian descents (stage 2). Logistic regression models were used to calculate adjusted ORs and 95% confidence intervals (CI) as a measure of the association of breast cancer risk and genetic variants.
RESULTS - Two SNPs were replicated in stage 2 at P < 0.05: rs1419026 at 6q14 [per allele OR, 1.07; 95% confidence interval (CI), 1.03-1.12; P = 3.0 × 10(-4)] and rs941827 at 10q25 (OR, 0.92, 95% CI, 0.89-0.96; P = 5.3 × 10(-5)). The association with rs941827 remained highly statistically significant after adjusting for the risk variant identified initially in women of European ancestry (OR, 0.88; 95% CI, 0.82-0.97; P = 5.3 × 10(-5)).
CONCLUSION - We identified a new breast cancer risk variant at 10q25 in East Asian women.
IMPACT - Results from this study improve the understanding of the genetic basis for breast cancer.
0 Communities
4 Members
0 Resources
16 MeSH Terms
Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia.
Lan Q, Hsiung CA, Matsuo K, Hong YC, Seow A, Wang Z, Hosgood HD, Chen K, Wang JC, Chatterjee N, Hu W, Wong MP, Zheng W, Caporaso N, Park JY, Chen CJ, Kim YH, Kim YT, Landi MT, Shen H, Lawrence C, Burdett L, Yeager M, Yuenger J, Jacobs KB, Chang IS, Mitsudomi T, Kim HN, Chang GC, Bassig BA, Tucker M, Wei F, Yin Z, Wu C, An SJ, Qian B, Lee VH, Lu D, Liu J, Jeon HS, Hsiao CF, Sung JS, Kim JH, Gao YT, Tsai YH, Jung YJ, Guo H, Hu Z, Hutchinson A, Wang WC, Klein R, Chung CC, Oh IJ, Chen KY, Berndt SI, He X, Wu W, Chang J, Zhang XC, Huang MS, Zheng H, Wang J, Zhao X, Li Y, Choi JE, Su WC, Park KH, Sung SW, Shu XO, Chen YM, Liu L, Kang CH, Hu L, Chen CH, Pao W, Kim YC, Yang TY, Xu J, Guan P, Tan W, Su J, Wang CL, Li H, Sihoe AD, Zhao Z, Chen Y, Choi YY, Hung JY, Kim JS, Yoon HI, Cai Q, Lin CC, Park IK, Xu P, Dong J, Kim C, He Q, Perng RP, Kohno T, Kweon SS, Chen CY, Vermeulen R, Wu J, Lim WY, Chen KC, Chow WH, Ji BT, Chan JK, Chu M, Li YJ, Yokota J, Li J, Chen H, Xiang YB, Yu CJ, Kunitoh H, Wu G, Jin L, Lo YL, Shiraishi K, Chen YH, Lin HC, Wu T, Wu YL, Yang PC, Zhou B, Shin MH, Fraumeni JF, Lin D, Chanock SJ, Rothman N
(2012) Nat Genet 44: 1330-5
MeSH Terms: Adenocarcinoma, Adenocarcinoma of Lung, Adult, Aged, Asian Continental Ancestry Group, Carcinoma, Squamous Cell, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lung Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, Smoking
Show Abstract · Added September 3, 2013
To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.
0 Communities
3 Members
0 Resources
20 MeSH Terms
Genome-wide meta-analyses of smoking behaviors in African Americans.
David SP, Hamidovic A, Chen GK, Bergen AW, Wessel J, Kasberger JL, Brown WM, Petruzella S, Thacker EL, Kim Y, Nalls MA, Tranah GJ, Sung YJ, Ambrosone CB, Arnett D, Bandera EV, Becker DM, Becker L, Berndt SI, Bernstein L, Blot WJ, Broeckel U, Buxbaum SG, Caporaso N, Casey G, Chanock SJ, Deming SL, Diver WR, Eaton CB, Evans DS, Evans MK, Fornage M, Franceschini N, Harris TB, Henderson BE, Hernandez DG, Hitsman B, Hu JJ, Hunt SC, Ingles SA, John EM, Kittles R, Kolb S, Kolonel LN, Le Marchand L, Liu Y, Lohman KK, McKnight B, Millikan RC, Murphy A, Neslund-Dudas C, Nyante S, Press M, Psaty BM, Rao DC, Redline S, Rodriguez-Gil JL, Rybicki BA, Signorello LB, Singleton AB, Smoller J, Snively B, Spring B, Stanford JL, Strom SS, Swan GE, Taylor KD, Thun MJ, Wilson AF, Witte JS, Yamamura Y, Yanek LR, Yu K, Zheng W, Ziegler RG, Zonderman AB, Jorgenson E, Haiman CA, Furberg H
(2012) Transl Psychiatry 2: e119
MeSH Terms: Adult, African Americans, Aged, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 15, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Nerve Tissue Proteins, Phenotype, Polymorphism, Single Nucleotide, Proteoglycans, Receptors, Nicotinic, Smoking, Statistics as Topic
Show Abstract · Added March 20, 2014
The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (β = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.
0 Communities
1 Members
0 Resources
21 MeSH Terms
A multistage genetic association study identifies breast cancer risk loci at 10q25 and 16q24.
Higginbotham KS, Breyer JP, McReynolds KM, Bradley KM, Schuyler PA, Plummer WD, Freudenthal ME, Trentham-Dietz A, Newcomb PA, Parl FF, Sanders ME, Page DL, Egan KM, Dupont WD, Smith JR
(2012) Cancer Epidemiol Biomarkers Prev 21: 1565-73
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Breast Neoplasms, Chromosome Mapping, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 16, Female, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Humans, Middle Aged, Polymorphism, Single Nucleotide, Risk
Show Abstract · Added March 7, 2014
BACKGROUND - Heritable risk for breast cancer includes an increasing number of common, low effect risk variants. We conducted a multistage genetic association study in a series of independent epidemiologic breast cancer study populations to identify novel breast cancer risk variants.
METHODS - We tested 1,162 SNPs of greatest nominal significance from stage I of the Cancer Genetic Markers of Susceptibility breast cancer study (CGEMS; 1,145 cases, 1,142 controls) for evidence of replicated association with breast cancer in the Nashville Breast Cohort (NBC; 599 cases, 1,161 controls), the Collaborative Breast Cancer Study (CBCS; 1,552 cases, 1,185 controls), and BioVU Breast Cancer Study (BioVU; 1,172 cases, 1,172 controls).
RESULTS - Among these SNPs, a series of validated breast cancer risk variants yielded expected associations in the study populations. In addition, we observed two previously unreported loci that were significantly associated with breast cancer risk in the CGEMS, NBC, and CBCS study populations and had a consistent, although not statistically significant, risk effect in the BioVU study population. These were rs1626678 at 10q25.3 near ENO4 and KIAA1598 (meta-analysis age-adjusted OR = 1.13 [1.07-1.20], P = 5.6 × 10(-5)), and rs8046508 at 16q23.1 in the eighth intron of WWOX (meta-analysis age-adjusted OR = 1.20 [1.10-1.31], P = 3.5 × 10(-5)).
CONCLUSIONS - Our data supports the association of two novel loci, at 10q25.3 and 16q23.1, with risk of breast cancer.
IMPACT - The expanding compendium of known breast cancer genetic risk variants holds increasing power for clinical risk prediction models of breast cancer, improving upon the Gail model.
©2012 AACR
0 Communities
4 Members
0 Resources
16 MeSH Terms
Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats.
Stankiewicz P, Kulkarni S, Dharmadhikari AV, Sampath S, Bhatt SS, Shaikh TH, Xia Z, Pursley AN, Cooper ML, Shinawi M, Paciorkowski AR, Grange DK, Noetzel MJ, Saunders S, Simons P, Summar M, Lee B, Scaglia F, Fellmann F, Martinet D, Beckmann JS, Asamoah A, Platky K, Sparks S, Martin AS, Madan-Khetarpal S, Hoover J, Medne L, Bonnemann CG, Moeschler JB, Vallee SE, Parikh S, Irwin P, Dalzell VP, Smith WE, Banks VC, Flannery DB, Lovell CM, Bellus GA, Golden-Grant K, Gorski JL, Kussmann JL, McGregor TL, Hamid R, Pfotenhauer J, Ballif BC, Shaw CA, Kang SH, Bacino CA, Patel A, Rosenfeld JA, Cheung SW, Shaffer LG
(2012) Hum Mutat 33: 165-79
MeSH Terms: Abnormalities, Multiple, Child, Child, Preschool, Chromosome Aberrations, Chromosome Mapping, Chromosomes, Human, Pair 10, DNA Copy Number Variations, Developmental Disabilities, Female, Genetic Variation, Homologous Recombination, Humans, In Situ Hybridization, Fluorescence, Infant, Intellectual Disability, Male, Nerve Growth Factors, Oligonucleotide Array Sequence Analysis, Penetrance, Segmental Duplications, Genomic, Sequence Deletion, Vesicular Acetylcholine Transport Proteins
Show Abstract · Added March 27, 2014
We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers.
© 2011 Wiley Periodicals, Inc.
0 Communities
1 Members
0 Resources
22 MeSH Terms
Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium.
Cai Q, Long J, Lu W, Qu S, Wen W, Kang D, Lee JY, Chen K, Shen H, Shen CY, Sung H, Matsuo K, Haiman CA, Khoo US, Ren Z, Iwasaki M, Gu K, Xiang YB, Choi JY, Park SK, Zhang L, Hu Z, Wu PE, Noh DY, Tajima K, Henderson BE, Chan KY, Su F, Kasuga Y, Wang W, Cheng JR, Yoo KY, Lee JY, Zheng H, Liu Y, Shieh YL, Kim SW, Lee JW, Iwata H, Le Marchand L, Chan SY, Xie X, Tsugane S, Lee MH, Wang S, Li G, Levy S, Huang B, Shi J, Delahanty R, Zheng Y, Li C, Gao YT, Shu XO, Zheng W
(2011) Hum Mol Genet 20: 4991-9
MeSH Terms: Adult, Aged, Alleles, Asia, Breast Neoplasms, Cell Line, Tumor, Chromosomes, Human, Pair 10, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Menopause, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide
Show Abstract · Added December 10, 2013
Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10(-9)). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.
0 Communities
5 Members
0 Resources
15 MeSH Terms
The novel atherosclerosis locus at 10q11 regulates plasma CXCL12 levels.
Mehta NN, Li M, William D, Khera AV, DerOhannessian S, Qu L, Ferguson JF, McLaughlin C, Shaikh LH, Shah R, Patel PN, Bradfield JP, He J, Stylianou IM, Hakonarson H, Rader DJ, Reilly MP
(2011) Eur Heart J 32: 963-71
MeSH Terms: Case-Control Studies, Chemokine CXCL12, Chromosomes, Human, Pair 10, Coronary Artery Disease, Enzyme-Linked Immunosorbent Assay, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors
Show Abstract · Added January 20, 2015
AIMS - Two single-nucleotide polymorphisms (SNPs), rs1746048 and rs501120, from genome wide association studies of coronary artery disease (CAD) map to chromosome 10q11 ∼80 kb downstream of chemokine CXCL12. Therefore, we examined the relationship between these two SNPs and plasma CXCL12 levels.
METHODS AND RESULTS - We tested the association of two SNPs with plasma CXCL12 levels in a two-stage study (n= 2939): first in PennCath (n= 1182), a Caucasian, angiographic CAD case-control study, and second in PennCAC (n= 1757), a community-based study of CAD risk factors. Plasma CXCL12 levels increased with age and did not vary by gender. There was no linkage disequilibrium between these two SNPs and SNPs within CXCL12 gene. However, CAD risk alleles at rs1746048 (C allele, P= 0.034; CC 2.33 ± 0.49, CT 2.27 ± 0.46, and TT 2.21 ± 0.52 ng/mL) and rs501120 (T allele, P= 0.041; TT 2.34 ± 0.49, CT 2.28 ± 0.46, and CC 2.23 ± 0.53 ng/mL) were associated with higher plasma levels of CXCL12 in age and gender adjusted models. In Stage 2, we confirmed this association (rs501120, T allele, P= 0.007), and meta-analysis strengthened this finding (n= 2939, P= 6.0 × 10(-4)). Finally, in exploratory analysis, the rs1746048 risk allele tended to have higher transcript levels of CXCL12 in human natural killer cells and the liver.
CONCLUSION - Coronary artery disease risk alleles downstream of CXCL12 are associated with plasma protein levels of CXCL12 and appear to be related to CXCL12 transcript levels in two human cell lines. This implicates CXCL12 as potentially causal and supports CXCL12 as a potential therapeutic target for CAD.
0 Communities
1 Members
0 Resources
13 MeSH Terms
Kindred with prominent corneal nerves associated with a mutation in codon 804 of RET on chromosome 10q11.
Ong DS, Lakhani V, Oates JA, O'Day DM
(2010) Arch Ophthalmol 128: 247-9
MeSH Terms: Aged, Carcinoma, Medullary, Chromosomes, Human, Pair 10, Codon, Cornea, Female, Humans, Male, Middle Aged, Multiple Endocrine Neoplasia Type 2a, Mutation, Ophthalmic Nerve, Pedigree, Proto-Oncogene Proteins c-ret, Thyroid Neoplasms, Young Adult
Added March 20, 2014
1 Communities
1 Members
0 Resources
16 MeSH Terms