Linkage disequilibrium analyses within chromosome 19p in multiple sclerosis

Objective The aim of this study was to determine if multiple sclerosis (MS) shows association with variants of single nucleotide polymorphisms (SNP) within chromosome 19p, where previous studies resulted in conflicting observations. Subjects and methods The transmissions of 569 SNP variants and 608 haplotypes from unaffected parents to their affected children were tested in 257 Caucasian families by using the pedigree disequilibrium test (PDT), the TRANSMIT version 2.5 program and the family- and haplotype-based association tests (FBAT and HBAT). The distribution of linkage disequilibrium (LD) among SNPs in 19p was assessed by ldmax and correlated with the location of MS-associated haplotypes. Results Individual SNP alleles did not show association after correction for multiple testing in PDT. Several marker haplotypes within potential candidate genes of intracellular enzymes, transmembrane proteins and receptors and signaling and adhesion molecules appeared to be weakly associated with the disease in both TRANSMIT and HBAT. However, none of the associations was strong enough to survive correction for multiple testing. Conclusions The present study is in the line of previous studies with negative conclusions concerning the role of the 19p region in MS. Multiple Sclerosis 2008; 14: 433—439. http://msj.sagepub.com

Investigation of the C242T polymorphism of NAD(P)H oxidase p22 phox gene and ischaemic heart disease using family-based association methods

Ischaemic heart disease is a complex phenotype arising from the interaction of genetic and environmental factors. Excessive production of reactive oxygen species leading to endothelial dysfunction is believed to be important in the pathogenesis of ischaemic heart disease. The NAD(P)H oxidase system generates superoxide anions in vascular cells; however, the role of the C242T polymorphism of the NAD(P)H oxidase p22 phox gene in ischaemic heart disease is unclear due to contradictory results from case-control studies. Consequently, we applied family-based association tests to investigate the role of this polymorphism in ischaemic heart disease in a well-defined Irish population. A total of 1023 individuals from 388 families (discordant sibships and parent/child trios) were recruited. Linkage disequilibrium between the polymorphism and ischaemic heart disease was tested using the combined transmission disequilibrium test (TDT)/sib-TDT (cTDT) and pedigree disequilibrium test (PDT). Both cTDT and PDT analyses found no statistically significant excess transmission of either allele to affected individuals (P=0.30 and P=0.28, respectively). Using robust family-based association tests specifically designed for the study of complex diseases, we found no evidence that the C242T polymorphism of the p22 phox gene has a significant role in the development of ischaemic heart disease in our population.