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Nonsynonymous Polymorphism (nonsynonymou + polymorphism)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Ala394Thr polymorphism in the clock gene NPAS2: A circadian modifier for the risk of non-Hodgkin's lymphoma

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2007
Yong Zhu
Abstract Circadian disruption is theorized to cause immune dysregulation, which is the only established risk factor for non-Hodgkin's lymphoma (NHL). Genes responsible for circadian rhythm are also involved in cancer-related biological pathways as potential tumor suppressors. However, no previous studies have examined associations between circadian genes and NHL risk. In this population-based case control study (n = 455 cases; 527 controls), we examined the only identified nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk. Our results demonstrate a robust association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with reduced risk of NHL (OR = 0.66, 95% CI: 0.51,0.85, p = 0.001), especially B-cell lymphoma (OR = 0.61, 95% CI: 0.47,0.80, p ,, 0.0001). These findings provide the first molecular epidemiologic evidence supporting a role of circadian genes in lymphomagenesis, which suggests that genetic variations in circadian genes might be a novel panel of promising biomarkers for NHL and warrants further investigation. © 2006 Wiley-Liss, Inc. [source]

A nonsynonymous polymorphism in IL23R gene is associated with risk of gastric cancer in a Chinese population,

MOLECULAR CARCINOGENESIS, Issue 10 2010
Jianjian Chen
Abstract Interleukin-23 receptor (IL-23R) is a key element in T helper (Th)17 cell-mediated inflammatory process, which plays an important role in pathogenesis of gastric cancer. Genetic variants of IL-23R have been identified as the predisposing factors for immunopathologic process. In this study, we hypothesized that the functional genetic variants of IL-23R gene may modify the risk of gastric cancer. To test this hypothesis, we conducted a case,control study including 1043 gastric cancer patients and 1089 controls in a Chinese population to assess the association between two potentially functional single nucleotide polymorphisms (SNPs) rs6682925 T>C and rs1884444 T>G of IL-23R and risk of gastric cancer. We found that the variant allele (G) of rs1884444 T>G, with amino acid His substituted by Gln at codon 3, was significantly associated with a decreased risk of gastric cancer [adjusted allelic odds ratio (OR),=,0.78, 95% confidence interval (CI),=,0.68,0.88]. In the stratified analysis, we found that this protective effect of rs1884444 G allele was mainly evident in intestinal-type gastric cancer (adjusted allelic OR,=,0.75, 95% CI,=,0.65,0.87) other than in diffuse-type gastric cancer (adjusted allelic OR,=,0.96, 95% CI,=,0.76,1.22). However, we did not find any significant association of rs6682925 T>C with gastric cancer risk. These findings indicate, for the first time, that the nonsynonymous variant rs1884444 T>G of IL-23R may contribute to gastric cancer susceptibility, especially in intestinal-type gastric cancer, in Chinese population. © 2010 Wiley-Liss, Inc. [source]

Phylogeography and speciation of colour morphs in the colonial ascidian Pseudodistoma crucigaster

MOLECULAR ECOLOGY, Issue 10 2004
I. TARJUELO
Abstract Variation in pigmentation is common in marine invertebrates, although few studies have shown the existence of genetic differentiation of chromatic forms in these organisms. We studied the genetic structure of a colonial ascidian with populations of different colour morphs in the northwestern Mediterranean. A fragment of the c oxidase subunit 1 (COI) mitochondrial gene was sequenced in seven populations of Pseudodistoma crucigaster belonging to three different colour morphs (orange, yellow and grey). Maximum likelihood analyses showed two well-supported clades separating the orange morph from the yellow-grey morphotypes. Genetic divergence between these clades was 2.12%, and ,ST values between populations of the two clades were high (average 0.936), pointing to genetic isolation. Nested clade and coalescence analyses suggest that a past fragmentation event may explain the phylogeographical origin of these two clades. Non-neutral mtDNA evolution is observed in our data when comparing the two clades, showing a significant excess of nonsynonymous polymorphism within the yellow,grey morphotype using the McDonald,Kreitman test, which is interpreted as further support of reproductive isolation. We conclude that the two clades might represent separate species. We compare the population genetic differentiation found with that estimated for other colonial and solitary ascidian species, and relate it to larval dispersal capabilities and other life-history traits. [source]

Toll-like receptor-1, -2, and -6 polymorphisms influence disease extension in inflammatory bowel diseases

INFLAMMATORY BOWEL DISEASES, Issue 1 2006
Marie Pierik MD
Abstract Background: Evidence that a deficient innate immune response toward the bacterial flora of the gut plays a role in the pathogenesis of inflammatory bowel disease (IBD) is growing. This is underscored by the finding of the association between CARD15 variants and Crohn's disease (CD) and D299G in Toll-like receptor (TLR) 4 and IBD. Our aims were to study nonsynonymous polymorphisms in other TLR genes in IBD. Methods: Thirty-five single nucleotide polymorphisms (SNP) in TLR1-10 were identified from public databases. 284 IBD parent-child trios and a second independent cohort of 285 IBD patients and 191 healthy controls were genotyped with polymerase chain reaction-restriction fragment length polymorphisms. Patients were pooled for genotype-phenotype analyses. Results: Although none of the SNPs was involved in disease susceptibility, a number of variants influenced the disease phenotype. A positive association between TLR1 R80T and pancolitis in UC (P = .045, OR [95% CI] 2.844 [1.026-7.844]) was found. The TLR2 R753G SNP was also associated with pancolitis (P = .027, OR [95% CI] 4.741 [1.197-18.773]). The relative risks for heterozygous patients to develop pancolitis were 5.8 and 3.3 for R80T and R753G, respectively. There was a negative association between TLR6 S249P and ulcerative colitis with proctitis only (P = .026, OR [95% CI] 0.223 [0.096-0.705]). In CD, we found a negative association between ileal disease involvement and TLR1 S602I (P = .03, OR [95% CI] 0.522 [0.286-0.950]). Conclusion:TLR2 and its cofactors TLR1 and TLR6 are involved in the initial immune response to bacteria by recognizing peptidoglycan. An association between nonsynonymous variants in the TLR1, - 2, and - 6 genes and extensive colonic disease in UC and CD was found. Our findings further highlight the role of an abnormal innate immune response in the pathogenesis of IBD. [source]

Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis

ARTHRITIS & RHEUMATISM, Issue 7 2008
Michelle L. Harris
Objective Protein citrullination is an important posttranslational modification recognized by rheumatoid arthritis (RA),specific autoantibodies. One of the citrullinating enzymes, peptidyl arginine deiminase type 4 (PAD-4), is genetically associated with development of RA in some populations, although the mechanism(s) mediating this effect are not yet clear. There have been descriptions of anti,PAD-4 autoantibodies in different rheumatic diseases. This study was undertaken to investigate whether anti,PAD-4 antibodies are specific to RA, are associated with disease phenotype or severity, and whether PAD-4 polymorphisms influence the anti,PAD-4 autoantibody response. Methods Sera from patients with established RA, patients with other rheumatic diseases, and healthy adults were assayed for anti,PAD-4 autoantibodies by immunoprecipitation of in vitro,translated PAD-4. The epitope(s) recognized by PAD-4 autoantibodies were mapped using various PAD-4 truncations. PAD-4 genotyping was performed on RA patients with the TaqMan assay. Joint erosions were scored from hand and foot radiographs using the Sharp/van der Heijde method. Results PAD-4 autoantibodies were found in 36,42% of RA patients, and were very infrequent in controls. Recognition by anti,PAD-4 autoantibodies required the 119 N-terminal amino acids, which encompass the 3 nonsynonymous polymorphisms associated with disease susceptibility. Strikingly, the anti,PAD-4 immune response was associated with the RA susceptibility haplotype of PADI4. Anti,PAD-4 antibodies were associated with more severe joint destruction in RA. Conclusion Our findings indicate that anti,PAD-4 antibodies are specific markers of RA, independently associated with more severe disease, suggesting that an anti,PAD-4 immune response may be involved in pathways of joint damage in this disease. Polymorphisms in the PADI4 gene influence the immune response to the PAD-4 protein, potentially contributing to disease propagation. [source]