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1.
Psoriasis is a chronic disease characterized by inflammation of the skin. The level of C-reactive protein (CRP), an inflammatory
marker that correlates well with the severity of psoriasis, is a heritable trait. This study aimed to assess the role of variations
in the CRP gene in patients with psoriasis among the Chinese-Taiwanese. In total, 305 patients with psoriasis and 615 control subjects
were analyzed for the presence of the CRP polymorphisms rs2794521, rs3091244, and rs1800947 by polymerase chain reaction.
The analysis revealed that neither polymorphism was found to be associated with psoriasis. No significant difference was observed
in the genotype and allele distribution for any of the individual CRP polymorphisms between the cases and the controls. The overall haplotype frequency profiles derived from the three polymorphisms
did not differ significantly between the cases and the controls. Our results suggest that these three CRP gene polymorphisms may not contribute to the genetic background of psoriasis in Chinese-Taiwanese. 相似文献
2.
Hai-Xiang Su Hai-Hong Zhou Ming-Yu Wang Jin Cheng Shi-Chao Zhang Feng Hui Xue-Zhong Chen Shan-Hui Liu Qin-Jiang Liu Zi-Jiang Zhu Qing-Rong Hu Yi Wu Shang-Rong Ji 《PloS one》2014,9(7)
C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or just represents a bystander marker. We have recently identified recurrent mutations at the SNP position -286 (rs3091244) in the promoter of CRP gene in several tumor types, instead suggesting that locally produced CRP is a potential driver of tumorigenesis. However, it is unknown whether the -286 site is the sole SNP position of CRP gene targeted for mutation and whether there is any association between CRP SNP mutations and other frequently mutated genes in tumors. Herein, we have examined the genotypes of three common CRP non-coding SNPs (rs7553007, rs1205, rs3093077) in tumor/normal sample pairs of 5 cancer types (n = 141). No recurrent somatic mutations are found at these SNP positions, indicating that the -286 SNP mutations are preferentially selected during the development of cancer. Further analysis reveals that the -286 SNP mutations of CRP tend to co-occur with mutated APC particularly in rectal cancer (p = 0.04; n = 67). By contrast, mutations of CRP and p53 or K-ras appear to be unrelated. There results thus underscore the functional importance of the -286 mutation of CRP in tumorigenesis and imply an interaction between CRP and Wnt signaling pathway. 相似文献
3.
Christian Gytz Ammitzb?ll Rudi Steffensen Martin B?gsted Kim H?rslev-Petersen Merete L Hetland Peter Junker Julia S Johansen Jan P?denphant Mikkel ?stergaard Torkell Ellingsen Kristian Stengaard-Pedersen 《Arthritis research & therapy》2014,16(5)
Introduction
Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Score in 28 joints (DAS28). We aimed to investigate the possible association between seven CRP SNPs, their haplotypes and the serum levels of CRP, as well as DAS28 scores, in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment.Methods
Overall, 315 patients with RA from two randomized controlled trials (the CIMESTRA and OPERA trials) who were naïve to disease-modifying antirheumatic drugs and steroids with disease durations less than 6 months were included. Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment.Results
The minor allele of rs1205 C > T was associated with decreased CRP levels at baseline (P = 0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P = 0.005) compared to homozygosity of the major allele, but no association was observed at year 1 (P = 0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P = 0.043), although no effect was observed at year 1 (P = 0.466). No other SNP or haplotype was associated with CRP at baseline or at year 1 (P ≥0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or at year 1 (P ≥0.10).Conclusion
CRP genotype and haplotype were only marginally associated with serum CRP levels and had no association with the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.Trial registration
The OPERA study is registered at Clinicaltrials.gov (). The CIMESTRA study is not listed in a clinical trials registry, because patients were included between October 1999 and October 2002. NCT00660647Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0475-3) contains supplementary material, which is available to authorized users. 相似文献4.
Rajkumar Dorajoo Ruoying Li Mohammad Kamran Ikram Jianjun Liu Philippe Froguel Jeannette Lee Xueling Sim Rick Twee-Hee Ong Wan Ting Tay Chen Peng Terri L. Young Alexandra I. F. Blakemore Ching Yu Cheng Tin Aung Paul Mitchell Jie Jin Wang Caroline C. Klaver Eric Boerwinkle Ronald Klein David S. Siscovick Richard A. Jensen Vilmundur Gudnason Albert Vernon Smith Yik Ying Teo Tien Yin Wong E-Shyong Tai Chew-Kiat Heng Yechiel Friedlander 《PloS one》2013,8(7)
Introduction
C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods
Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results
Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10−8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions
Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease. 相似文献5.
Caitrin W. McDonough Pamela J. Hicks Lingyi Lu Carl D. Langefeld Barry I. Freedman Donald W. Bowden 《Human genetics》2009,126(2):265-275
Four genome wide linkage scans for diabetic nephropathy have mapped susceptibility loci to chromosome 18q22.3-23 in the region
of the carnosinase genes, CNDP1 and CNDP2. CNDP1 has been associated with diabetic nephropathy in Europeans and European Americans, but not African-Americans. Individuals
homozygous for a five tri-nucleotide repeat allele (5L; D18S880) are protected from diabetic nephropathy. We identified 64
variants after sequencing the exons, promoter, and 3′ UTR of CNDP1 and CNDP2 in African-American and European American DNA samples. After scanning 44 of these variants, extensive genotyping of 12 SNPs
and D18S880 was performed in 1,025 African-American cases with type 2 diabetes (DM)-associated end-stage renal disease (ESRD)
and 1,064 African-American non-diabetic non-nephropathy controls to assess whether the carnosinase genes influence risk for
DM-ESRD in African-Americans. Evidence of association with DM-ESRD was seen with 2 SNPs: rs6566810 and rs4892247; 3 two-marker
haplotypes: rs6566810 and rs17089362, rs17089362 and rs890336, and rs890334 and rs12717111 (global empirical P = 0.0034, 0.0275, and 0.0002, respectively) and 3 three-marker haplotypes: rs6566810, rs17089362, and rs890336; rs890335,
rs890334, and rs12717111; and rs890334, rs12717111, and D18S880 (global empirical P = 0.0074, 1.5E-05, and 0.0032, respectively). The risk haplotypes (rs6566810, rs17089362 [A,T] and rs6566810, rs17089362,
rs890336 [A,T,C]) were most strongly associated with DM-ESRD among African-Americans in the non 5L–5L group. Variants in the
carnosinase genes appear to contribute to diabetic nephropathy susceptibility in African-Americans. Protection from diabetic
nephropathy afforded by 5L–5L homozygosity in CNDP1 may be masked by the effects of additional risk haplotypes in CNDP1 and CNDP2.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
6.
Laura J. Rasmussen-Torvik James S. Pankow David R. JacobsJr Julia Steinberger Antoinette Moran Alan R. Sinaiko 《Human genetics》2009,125(1):21-28
Few studies have examined the association of SNPs in the adiponectin (ADIPOQ) and adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2)
genes with the euglycemic clamp, i.e. the gold standard measure of insulin sensitivity. The association of comprehensive tag
SNPs in these genes with insulin sensitivity was examined in a cohort of adolescents and their parents. Probands and siblings
(n = 441, mean age = 17.9 years) were recruited along with their parents (n = 262, mean age = 47.9 years). Typed SNPs included 21 SNPs in ADIPOQ, 7 SNPs in ADIPOR1, and 13 SNPs in ADIPOR2. Mixed model
linear regression was used to test the association of SNPs with euglycemic-clamp derived insulin sensitivity. All analyses
were stratified by race. After corrections to account for multiple testing and the linkage disequilibrium structure of the
genes, one SNP in the ADIPOQ gene (rs822393) was significantly associated with insulin sensitivity in white subjects. In whites,
six SNPs in ADIPOQ, one SNP in ADIPOR1 and one SNP in ADIPOR2 were associated with insulin sensitivity at the P < 0.05 level. In African Americans, two SNPs in ADIPOR1 were associated with insulin sensitivity at the P < 0.05 level. These results suggest that a variant in the ADIPOQ gene influences levels of insulin sensitivity and age may
modify the effects of this variant. There are several other variants in ADIPOQ, ADIPOR1, and ADIPOR2 that may influence insulin
sensitivity and these variants should be further investigated in other populations.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
7.
Leak TS Mychaleckyj JC Smith SG Keene KL Gordon CJ Hicks PJ Freedman BI Bowden DW Sale MM 《Human genetics》2008,124(1):63-71
Previously, we performed a genome scan for type 2 diabetes (T2DM) using 638 African-American (AA) affected sibling pairs from
247 families; non-parametric linkage analysis suggested evidence of linkage at 6q24–27 (LOD 2.26). To comprehensively evaluate
this region, we performed a two-stage association study by first constructing a SNP map of 754 SNPs selected from HapMap on
the basis of linkage disequilibrium (LD) in 300 AAT2DM end-stage renal disease (ESRD) subjects, 311 AA controls, 43 European
American controls and 45 Yoruba Nigerian samples (Set 1). Replication analyses were conducted in an independent population
of 283 AA T2DM-ESRD subjects and 282 AA controls (Set 2). In addition, we adjusted for the impact of admixture on association
results by using ancestry informative markers (AIMs). In Stage 1, 137 (18.2%) SNPs showed nominal evidence of association
(P < 0.05) in one or more of tests of association: allelic (n = 33), dominant (n = 36), additive (n = 29), or recessive (n = 34) genotypic models, and 2- (n = 47) and 3-SNP (n = 43) haplotypic analyses. These SNPs were selected for follow-up genotyping. Stage 2 analyses confirmed association with
a predicted 2-SNP “risk” haplotype in the PARK2 gene. Also, two intergenic SNPs showed consistent genotypic association with T2DM-ESRD: rs12197043 and rs4897081. Combined
analysis of all subjects from both stages revealed nominal associations with 17 SNPs within genes, including suggestive associations
in ESR1 and PARK2. This study confirms known diabetic nephropathy loci and identifies potentially novel susceptibility variants located within
6q24–27 in AA.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
8.
Caitrin W. McDonough Meredith A. Bostrom Lingyi Lu Pamela J. Hicks Carl D. Langefeld Jasmin Divers Josyf C. Mychaleckyj Barry I. Freedman Donald W. Bowden 《Human genetics》2009,126(6):805-817
Genetic studies in Turkish, Native American, European American, and African American (AA) families have linked chromosome
18q21.1–23 to susceptibility for diabetes-associated nephropathy. In this study, we have carried out fine linkage mapping
in the 18q region previously linked to diabetic nephropathy in AAs by genotyping both microsatellite and single nucleotide
polymorphisms (SNPs) for linkage analysis in an expanded set of 223 AA families multiplexed for type 2 diabetes associated
ESRD (T2DM-ESRD). Several approaches were used to evaluate evidence of linkage with the strongest evidence for linkage in
ordered subset analysis with an earlier age of T2DM diagnosis compared to the remaining pedigrees (LOD 3.9 at 90.1 cM, ∆P = 0.0161, NPL P value = 0.00002). Overall, the maximum LODs and LOD-1 intervals vary in magnitude and location depending upon analysis. The
linkage mapping was followed up by performing a dense SNP map, genotyping 2,814 SNPs in the refined LOD-1 region in 1,029
AA T2DM-ESRD cases and 1,027 AA controls. Of the top 25 most associated SNPs, 10 resided within genic regions. Two candidate
genes stood out: NEDD4L and SERPINB7. SNP rs512099, located in intron 1 of NEDD4L, was associated under a dominant model of inheritance [P value = 0.0006; Odds ratio (95% Confidence Interval) OR (95% CI) = 0.70 (0.57–0.86)]. SNP rs1720843, located in intron 2
of SERPINB7, was associated under a recessive model of inheritance [P value = 0.0017; OR (95% CI) = 0.65 (0.50–0.85)]. Collectively, these results suggest that multiple genes in this region may
influence diabetic nephropathy susceptibility in AAs. 相似文献
9.
Sheng Wei Zhensheng Liu Yangkai Li Li‐E Wang Wei V. Chen Christopher I. Amos Jeffrey E. Lee Mark M. Iles Matthew H. Law Anne E. Cust Jennifer H. Barrett Grant W. Montgomery John Taylor Julia A. Newton Bishop Stuart MacGregor D. Timothy Bishop Graham J. Mann Nicholas K. Hayward Qingyi Wei 《Pigment cell & melanoma research》2013,26(3):392-401
To mine possibly hidden causal single‐nucleotide polymorphisms (SNPs) of melanoma, we investigated the association of SNPs in 76 M/G1 transition genes with melanoma risk using our published genome‐wide association study (GWAS) data set with 1804 melanoma cases and 1026 cancer‐free controls. We found multiple SNPs with P < 0.01 and performed validation studies for 18 putative functional SNPs in PSMB9 in two other GWAS data sets. Two SNPs (rs1351383 and rs2127675) were associated with melanoma risk in the GenoMEL data set (P = 0.013 and 0.004, respectively), but failed in validation using the Australian data set. Genotype–phenotype analysis revealed these two SNPs were significantly correlated with mRNA expression level of PSMB9. Further experiments revealed that SNP rs2071480, which is in high LD with rs1351383 and rs2127675, may have a weak effect on the promoter activity of PSMB9. Taken together, our data suggested that functional variants in PSMB9 may contribute to melanoma susceptibility. 相似文献
10.
11.
Keene KL Mychaleckyj JC Smith SG Leak TS Perlegas PS Langefeld CD Herrington DM Freedman BI Rich SS Bowden DW Sale MM 《Human genetics》2008,123(4):333-341
We previously investigated the estrogen receptor α gene (ESR1) as a positional candidate for type 2 diabetes (T2DM), and found
evidence for association between the intron 1-intron 2 region of this gene and T2DM and/or nephropathy in an African American
(AA) population. Our objective was to comprehensively evaluate variants across the entire ESR1 gene for association in AA
with T2DM and end stage renal disease (T2DM–ESRD). One hundred fifty SNPs in ESR1, spanning 476 kb, were genotyped in 577
AA individuals with T2DM–ESRD and 596 AA controls. Genotypic association tests for dominant, additive, and recessive models,
and haplotypic association, were calculated using a χ2 statistic and corresponding P value. Thirty-one SNPs showed nominal evidence for association (P < 0.05) with T2DM–ESRD in one or more genotypic model. After correcting for multiple tests, promoter SNP rs11964281 (nominal
P = 0.000291, adjusted P = 0.0289), and intron 4 SNPs rs1569788 (nominal P = 0.000754, adjusted P = 0.0278) and rs9340969 (nominal P = 0.00109, adjusted P = 0.0467) remained significant at experimentwise error rate (EER) P ≤ 0.05 for the dominant class of tests. Twenty-three of the thirty-one associated SNPs cluster within the intron 4–intron
6 regions. Gender stratification revealed nominal evidence for association with 35 SNPs in females (352 cases; 306 controls)
and seven SNPs in males (225 cases; 290 controls). We have identified a novel region of the ESR1 gene that may contain important
functional polymorphisms in relation to susceptibility to T2DM and/or diabetic nephropathy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
12.
Jun Bian Zhenjian Zhuo Jinhong Zhu Zhonghua Yang Zhang Jiao Yong Li Jiwen Cheng Haixia Zhou Suhong Li Li Li Jing He Yanfei Liu 《Journal of cellular and molecular medicine》2020,24(16):9280-9286
Neuroblastoma ranks as the most commonly seen and deadly solid tumour in infancy. The aberrant activity of m6A‐RNA methyltransferase METTL3 is involved in human cancers. Therefore, functional genetic variants in the METTL3 gene may contribute to neuroblastoma risk. In the current nine‐centre case‐control study, we aimed to analyse the association between the METTL3 gene single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We genotyped four METTL3 gene SNPs (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G, and rs1263801 G>C) in 968 neuroblastoma patients and 1814 controls in China. We found significant associations between these SNPs and neuroblastoma risk in neither single‐locus nor combined analyses. Interestingly, in the stratified analysis, we observed a significant risk association with rs1061027 AA in subgroups of children ≤ 18 months of age (adjusted OR = 1.87, 95% CI = 1.03‐3.41, P = .040) and females (adjusted OR = 1.86, 95% CI = 1.07‐3.24, P = .028). Overall, we identified a significant association between METTL3 gene rs1061027 C>A polymorphism and neuroblastoma risk in children ≤18 months of age and females. Our findings provide novel insights into the genetic determinants of neuroblastoma. 相似文献
13.
Ying-Erh Chou Ming-Ju Hsieh Shian-Shiang Wang Chia-Yen Lin Yen-Yu Chen Yung-Chuan Ho Shun-Fa Yang 《Journal of cellular and molecular medicine》2021,25(22):10761-10769
The receptor for advanced glycation end products (RAGE) overexpression was suggested to be associated with prostate cancer development and poor prognosis. In this study, we focused on the correlations between the clinicopathological characteristics and susceptibility of prostate cancer and RAGE single-nucleotide polymorphisms (SNPs). In 579 prostate cancer patients, the RAGE SNPs rs1800625, rs1800624, rs2070600 and rs184003 in patients with or without grade group upgrade were analysed with real-time polymerase chain reaction. The results demonstrated that the prostate cancer patients who carried the RAGE SNPs rs2070600 ‘GA’ genotypic variants were significantly associated with lower risk to develop grade group upgrade. Moreover, patients with the RAGE rs1800625 ‘TC + CC’ genotypic variants were associated with higher risk of perineural invasion. In 343 prostate cancer patients who carried the RAGE rs1800625 ‘TC + CC’ genotype without grade group upgrade were correlated with higher risk of biochemical recurrence and perineural invasion. In the analysis of TCGA database, significant differences of the RAGE mRNA level were found between the normal controls and prostate cancer patients (p < 0.0001), and the pathologic stage N1 and N0 patients (p = 0.0027). The prostate cancer patients with high RAGE expression were associated with lower overall survival rate (p = 0.025). In conclusion, our results have revealed that the RAGE SNPs rs2070600 and rs1800625 were associated with the grade group upgrade of prostate cancer and clinical status. The RAGE polymorphisms may provide as a pivotal predictor to evaluate prostate cancer disease progression and prognosis. 相似文献
14.
《Cytokine》2016
Overweight and obesity are associated with chronic and subclinical inflammation due to an imbalance of inflammatory mediators. However, the association with gene polymorphism has been rarely studied in children. The aim of this study was to determine if serum concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) are related to the IL6 rs1800795, IL6 rs2069845 and CRP rs1205 polymorphisms (SNPs) according to body mass index (BMI) in a sample of children and adolescents. A cross-sectional study in 470 students between 7 and 17 years of age of anthropometric characteristics, high sensitivity-CRP (Hs-CRP) and IL-6 levels and three SNPs genotyped. The prevalence ratio of hs-CRP > 3 mg/L in obese individuals was 4.15 (CI 2.43–7.06; p = 0.01), and it was 1.91 (CI 1.03–3.55; p = 0.03) in overweight individuals and 1.74 (CI 1.05–2.88 p = 0.03) in females. Individuals with waist circumference (WC) and body fat percentage (BF%) alterations showed elevated levels of hs-CRP (p = 4.3 × 10−5 and p = 5.3 × 10−6). The combination of any two anthropometric measurement increases CRP levels, especially combinations with obesity body mass index (BMI): BMI + WC and BMI + BF%. Among the overweight/obesity group, T allele carriers of CRP rs1205 showed lower levels of hs-CRP (0.5, IQR = 0.3–1.8 mg/L) than CC homozygotes (1.5, IQR = 0.4–3.4 mg/L, p = 0.018). Additionally, considering subjects with two or three anthropometric alterations for CRP rs1205: rs1205 T allele carriers had lower levels of hs-CRP (0.7, IQR = 0.3–2.7 mg/L) than CC homozygotes (1.2, IQR = 0.5–3.5 mg/L, p = 0.02). In conclusion, carriers of the rs1205/T allele with higher BMIs had lower levels of hs-CRP. Schoolchildren who were overweight/obese had higher levels of CRP and IL-6, whereas individuals with WC and BF% alterations had higher levels of CRP. 相似文献
15.
To replicating the associations of type 2 diabetes (T2D) and six novel reported variants in Han Chinese lean individuals of
first episode T2D, a total of six high risk single nucleotide polymorphisms (SNPs) from the BCL11A, DUSP9, IRS1, CENTD2, ADRA2A, and CDKAL1 genes were examined. Candidate six SNPs were genotyped in 761 T2D patients and 433 control subjects, and associations between
the six SNPs and Body Mass Index (BMI), Fasting Plasma Glucose (FPG) and Two Hours Oral Glucose Tolerance Test (2hOGTT) were
also investigated. CDKAL1 provided the strongest evidence for replication, where rs7754840 was associated with T2D (odds ratio = 1.54, per copy of
the risk C allele, P = 8.10 × 10−7). SNP rs5945326 at DUSP9 showed modest significance (odds ratio = 0.81, per copy of the protective G allele, P = 0.02). After adjusting the confounders of age, gender and BMI, the above results remain significant for both rs7754840
(P < 1.0 × 10−4) and rs5945326 (P = 0.043) respectively. After correcting for multiple testing, however, only the association between T2D and rs7754840 at
CDKAL1 (P < 1×10−4) remains significant. In addition, the risk C allele of CDKAL1 rs7754840 was significantly associated with increased FPG levels (P = 3.8 × 10−4). The association between genetic variant in CDKAL1 gene was detected in the Han Chinese lean individuals. The correlation between rs7754840-C allele and increased FPG levels
is consistent with the potential function of CDKAL1 gene in pancreatic islets. 相似文献
16.
Ruiz-Narvaez EA Fraser PA Palmer JR Cupples LA Reich D Wang YA Rioux JD Rosenberg L 《Human genetics》2011,130(6):807-815
The major histocompatibility complex (MHC) on chromosome 6p21 is a key contributor to the genetic basis of systemic lupus
erythematosus (SLE). Although SLE affects African Americans disproportionately compared to European Americans, there has been
no comprehensive analysis of the MHC region in relationship to SLE in African Americans. We conducted a screening of the MHC
region for 1,536 single nucleotide polymorphisms (SNPs) and the deletion of the C4A gene in a SLE case–control study (380 cases, 765 age-matched controls) nested within the prospective Black Women’s Health
Study. We also genotyped 1,509 ancestral informative markers throughout the genome to estimate European ancestry to control
for population stratification due to population admixture. The most strongly associated SNP with SLE was the rs9271366 (odds
ratio, OR = 1.70, p = 5.6 × 10−5) near the HLA-DRB1 gene. Conditional haplotype analysis revealed three other SNPs, rs204890 (OR = 1.86, p = 1.2 × 10−4), rs2071349 (OR = 1.53, p = 1.0 × 10−3), and rs2844580 (OR = 1.43, p = 1.3 × 10−3), to be associated with SLE independent of the rs9271366 SNP. In univariate analysis, the OR for the C4A deletion was 1.38, p = 0.075, but after simultaneous adjustment for the other four SNPs the odds ratio was 1.01, p = 0.98. A genotype score combining the four newly identified SNPs showed an additive risk according to the number of high-risk
alleles (OR = 1.67 per high-risk allele, p < 0.0001). Our strongest signal, the rs9271366 SNP, was also associated with higher risk of SLE in a previous Chinese genome-wide
association study (GWAS). In addition, two SNPs found in a GWAS of European ancestry women were confirmed in our study, indicating
that African Americans share some genetic risk factors for SLE with European and Chinese subjects. In summary, we found four
independent signals in the MHC region associated with risk of SLE in African American women. 相似文献
17.
18.
Lyle G. Best Richa Saxena Cindy M. Anderson Michael R. Barnes Hakon Hakonarson Gilbert Falcon Candelaria Martin Berta Almoguera Castillo Ananth Karumanchi Kylie Keplin Nichole Pearson Felicia Lamb Shellee Bercier Brendan J. Keating 《PloS one》2013,8(8)
Background
The etiology of pre-eclampsia (PE) is unknown; but it is accepted that normal pregnancy represents a distinctive challenge to the maternal immune system. C-reactive protein is a prominent component of the innate immune system; and we previously reported an association between PE and the CRP polymorphism, rs1205. Our aim was to explore the effects of additional CRP variants. The IBC (Cardiochip) genotyping microarray focuses on candidate genes and pathways related to the pathophysiology of cardiovascular disease.Methods
This study recruited 140 cases of PE and 270 matched controls, of which 95 cases met criteria as severe PE, from an American Indian community. IBC array genotypes from 10 suitable CRP SNPs were analyzed. A replication sample of 178 cases and 427 controls of European ancestry was also genotyped.Results
A nominally significant difference (p value <0.05) was seen in the distribution of discordant matched pairs for rs3093068; and Bonferroni corrected differences (P<0.005) were seen for rs876538, rs2794521, and rs3091244. Univariate conditional logistic regression odds ratios (OR) were nominally significant for rs3093068 and rs876538 models only. Multivariate logistic models with adjustment for mother''s age, nulliparity and BMI attenuated the effect (OR 1.58, P = 0.066, 95% CI 0.97–2.58) for rs876538 and (OR 2.59, P = 0.050, 95% CI 1.00–6.68) for rs3093068. An additive risk score of the above two risk genotypes shows a multivariate adjusted OR of 2.04 (P = 0.013, 95% CI 1.16–3.56). The replication sample also demonstrated significant association between PE and the rs876538 allele (OR = 1.55, P = 0.01, 95% CI 2.16–1.10). We also show putative functionality for the rs876538 and rs3093068 CRP variants.Conclusion
The CRP variants, rs876538 and rs3093068, previously associated with other cardiovascular disease phenotypes, show suggestive association with PE in this American Indian population, further supporting a possible role for CRP in PE. 相似文献19.
Genetic variants of nuclear factor erythroid‐derived 2‐like 2 associated with the complications in Han descents with type 2 diabetes mellitus of Northeast China
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Xiaohong Xu Jing Sun Xiaomin Chang Ji Wang Manyu Luo Kupper A. Wintergerst Lining Miao Lu Cai 《Journal of cellular and molecular medicine》2016,20(11):2078-2088
20.
Zheng X Ren W Zhang S Liu J Li S Li J Yang P He J Su S Li P 《Molecular biology reports》2012,39(1):17-23
TCF7L2 and SLC30A8 have been found to be associated with type 2 diabetes mellitus (T2DM) as well as with impaired proinsulin
processing recently, enzymes encoded by PCSK1 and PCSK2 are reported to play an important role in the process of proinsulin
conversion. To investigate whether the single nucleotide polymorphisms (SNPs) of TCF7L2, SLC30A8, PCSK1 and PCSK2 were associated
with T2DM as well as with proinsulin conversion in a Han Chinese population from Chongqing. A case–control study was performed
in Han Chinese subjects with normal control (n = 152) and T2DM (n = 227), we genotyped rs7903146 and rs11196218 at TCF7L2, rs13266634 at SLC30A8, rs3811951 at PCSK1 and rs2021785 at PCSK2.
Plasma levels of proinsulin were measured with an Enzyme Linked Immunosorbent Assay (ELISA). Genotype distribution and associations
with T2DM and fasting levels of proinsulin and proinsulin/insulin ratios were analyzed. We confirmed the association of risk
allele of rs2021785 at PCSK2 with type 2 diabetes also existed in Han Chinese population [OR = 1.4489 with 95% CI (1.0285,
2.0412), P = 0.0335]. Rs13266634 at SLC30A8 had a tendency to be associated with fasting plasma levels of proinsulin (P = 0.0639 in additive model). We did not find the significant association between other SNPs and T2DM or fasting levels of
proinsulin or proinsulin/insulin ratios. Our results provide evidence that the association of PCSK2 and T2DM was also existed
in Han Chinese population in Chongqing. We were underpowered to detect the association between other SNPs and T2DM or proinsulin
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