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Important Candidate Genes (important + candidate_gene)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Interleukin 10 (IL-10) gene variants and susceptibility for paediatric onset Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009
D. K. AMRE
Summary Background, A recent genome-wide association study in adult patients with ulcerative colitis (UC) has implicated the interleukin 10 (IL-10) gene as an important candidate gene. Moreover, a UC-associated single nucleotide polymorphism (SNP) rs3024405 was also significantly associated with adult Crohn's disease (CD). Aims, To examine whether IL-10 -CD associations extended to paediatric-onset CD. Methods, We implemented the case-control design at three paediatric gastroenterology clinics in Canada. CD patients (,20 years) were recruited along with healthy controls. DNA samples were genotyped for tag-single nucleotide polymorphisms (tag-SNPs) in the IL-10 gene. Allelic, genotype and haplotype associations with CD were studied. Results, A total of 270 patients and 336 controls were studied. The mean age (±s.d.) at diagnosis was 12.1 (±3.5). There were a slightly higher proportion of male patients (56.3%). Of the five IL-10 tag-SNPs, rs2222202 (C/T) (P = 0.03) and rs1800871 (C/T) (P = 0.05) showed significant allelic associations with CD. Specific IL-10 SNPs were associated with CD disease location and/or disease behaviour. Conclusions, Our gene-wide analysis replicates recent findings of associations between IL-10 and adult CD, and suggests that these associations extend to paediatric-onset CD as well. [source]

Differentiation of Caucasians and Chinese at Bone Mass Candidate Genes: Implication for Ethnic Difference of Bone Mass

ANNALS OF HUMAN GENETICS, Issue 3 2003
V. Dvornyk
Summary Bone mineral density (BMD) is an important risk factor for osteoporosis and has strong genetic determination. While average BMD differs among major ethnic groups, several important candidate genes have been shown to underlie BMD variation within populations of the same ethnicity. To investigate whether important candidate genes may contribute to ethnic differences in BMD, we studied the degree of genetic differentiation among several important candidate genes between two major ethnic groups: Caucasians and Chinese. The genetic variability of these two populations (1131 randomly selected individuals) was studied at six restriction sites exhibiting polymorphisms of five important candidate genes for BMD: the BsaHI polymorphism of the calcium-sensing receptor (CASR) gene, the SacI polymorphism of the ,2HS-glycoprotein (AHSG) gene, the PvuII and XbaI polymorphisms of the estrogen receptor , (ESR1) gene, the ApaI polymorphism of the vitamin D receptor (VDR) gene, and the BstBI polymorphism of the parathyroid hormone (PTH) gene. The two ethnic groups showed significant allelic and genotypic differentiation of all the polymorphisms studied. The mean FST was 0.103, which significantly differed from zero (P < 0.01). The Chinese population had lower mean heterozygosity (0.331) than the Caucasian one (0.444); the CASR - BsaHI and PTH - BstBI polymorphisms contributed most significantly to this difference. Analysis of the intra- and inter-population variability suggests that various types of natural selection may affect the observed patterns of variation at some loci. If some of the candidate genes we studied indeed underlie variation in BMD, their population differentiation revealed here between ethnic groups may contribute to understanding ethnic difference in BMD. [source]

Hip geometry variation is associated with bone mineralization pathway gene variants: The framingham study

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2010
Ching-Lung Cheung
Abstract Mineralization of bone matrix is an important process in bone formation; thus defects in mineralization have been implicated in bone mineral density (BMD) and bone structure alterations. Three central regulators of phosphate balance, ALPL, ANKH, and ENPP1, are central in the matrix mineralization process; therefore, the genes encoding them are considered important candidates genes for BMD and bone geometry. To test for an association between these three candidate genes and BMD and bone geometry traits, 124 informative single-nucleotide polymorphisms (SNPs) were selected and genotyped in 1513 unrelated subjects from the Framingham offspring cohort. Initial results showed that SNP rs1974201 in the gene ENPP1 was a susceptibility variant associated with several hip geometric indices, with the strongest p value of 3.8,×,10,7 being observed for femoral neck width. A few modest associations were observed between SNPs in or near ALPL and several bone traits, but no association was observed with ANKH. The association signals observed for SNPs around rs1974201 were attenuated after conditional analysis on rs1974201. Transcription factor binding-site prediction revealed that the HOXA7 binding site was present in the reference sequence with the major allele, whereas this potential binding site is lost in the sequence with the minor allele of rs1974201. In conclusion, we found evidence for association of bone geometry variation with an SNP in ENPP1, a gene in the mineralization pathway. The alteration of a binding site of the deregulator of extracellular matrix HOXA7 warrants further investigation. © 2010 American Society for Bone and Mineral Research [source]