Integration of sequence data from a consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10-6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. © 2014 Plenge et al

Antioxidant Activities of á-Tocopherol, Herbalox and Butylhydroxytoluene in Palm Olein Systems

This study was carried out to determine possible synergism and antagonism in blends of natural and synthetic antioxidants for protection of palm olein at high temperatures. Three primary antioxidants: (±)-á-tocopherol (Vitamin E), Rosemary extract (Herbalox) and butylated hydroxytoluene (BHT) were used in a mixture experiment for the protection of palm olein at steaming and frying temperatures. Results showed that palm olein was composed of 61.3% and 21.2% of oleic and linoleic acids respectively. Iodine value, unsaturated/saturated ratio and diene equivalent were 54.14, 4.9 and 22.89, respectively. The antioxidants protected palm olein against oxidation to different degrees in the following order: Butylated hydroxyl toluene > Rosemary extract > á-tocopherol at concentrations of 0.1% of the oil. The antioxidant protection factors were 1.63, 1.40 and 0.96 for butylated hydroxyltoluene, Rosemary extract and á-tocopherol respectively. Antioxidant synergism was observed in combinations of vitamin E/butylated hydroxyltoluene, and Rosemary extract/butylated hydroxyltoluene but antagonism was observed in vitamin E/ Rosemary extract. The findings of this study showed that Rosemary extract and butylated hydroxyltoluene and their mixtures are observed to be better antioxidants than vitamin E and their combinations with vitamin E in palm olein systems at 110oC