BACKGROUND Common variants of the renin-angiotensin system (RAS) genes have been linked to a higher risk of coronary artery disease (CAD) and its complications. AIM To determine the prognostic significance of a combination of three common polymorphisms of RAS genes (angiotensin converting enzyme - ACE Ins/Del, angiotensin receptor type 1 - AGT1R A1166C and angiotensinogen - ATG M235T) in pati...

Population level evolutionary processes can occur within a single organism when the germ line contains a mutation that confers a cost at the level of the cell. Here we describe how multiple compensatory mutations arose through a within-individual evolutionary process in two brothers with the immune deficiency Wiskott-Aldrich Syndrome (WAS). As a result, both brothers have T lymphocyte populatio...

Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 5...

PURPOSE BIM is essential for the response to tyrosine-kinase inhibitors (TKI) in chronic myeloid leukaemia (CML) patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutat...

A polymorphism in the promoter of human NRAMP1 encodes a Z-DNA forming dinucleotide repeat with four alleles: (1) t(gt)5ac(gt)5ac(gt)11g; (2) t(gt)5ac(gt)5 ac(gt)10g; (3) t(gt)5ac(gt) ac(gt)9g; and (4) t(gt)5ac(gt)9g. Alleles 1 and 4 are rare (gene frequencies approximately 0.001); alleles 2 and 3 occur at gene frequencies approximately 0.20-0.25 and approximately 0.75-0.80, respectively. Here,...

OBJECTIVES To explore the functional basis for the association between ankylosing spondylitis (AS) and single-nucleotide polymorphisms (SNPs) in the IL23R-IL12RB2 intergenic region. METHODS We performed conditional analysis on genetic association data and used epigenetic data on chromatin remodelling and transcription factor (TF) binding to identify the primary AS-associated IL23R-IL12RB2 int...

Usher syndrome type IC is a rare, autosomal recessive sensorineural disorder caused by mutations in the USH1C gene, which encodes a PDZ-domain protein named harmonin. The Acadian-specific 216G-->A mutation in exon 3 and a variant 9-repeat VNTR allele (designated VNTR(t,t)) in intron 5 are in complete linkage disequilibrium. (The usual form of the allele is referred to as VNTR(t).) To gain insig...

Synaptic transmission and plasticity mediated by NMDA receptors (NMDARs) could modulate the severity of multiple sclerosis (MS). Here the role of NMDARs in MS was first explored in 691 subjects carrying specific allelic variants of the NR1 subunit gene or of the NR2B subunit gene of this glutamate receptor. The analysis was replicated for significant SNPs in an independent sample of 1548 MS sub...

We evaluate the association between genetic polymorphisms of XRCC5 VNTR, XRCC6 -61C>G, and XRCC7 6721G>T with male infertility susceptibility. A total of 392 men including 178 infertile males (102 idiopathic azoospermia and 76 severe oligozoospermia) and 214 healthy controls were recruited. XRCC6 -61C>G and XRCC7 6721G>T genotyping was performed by PCR-RFLP whereas XRCC5 VNTR was performed by P...