−237A homozygosity associates with reduced TNFα production in PMA-activated B cell lines.

<p>(a) Immortalised BCL lines generated from healthy donors who were −237 AA homozygous (n = 4), −237GG homozygous (n = 11) or GA heterozygous (n = 4) were stimulated for 4 hours with PMA, or left untreated, following which mRNA was isolated for qPCR analysis. TNFα mRNA fold induction (stimulated/non-stimulated) is reported. (b) One million BCLs from −237GG homozygous (n = 11) and GA heterozygous (n = 4) donors were stimulated with PMA for 4 hours, following which soluble TNFα (sTNFα) levels were measured by ELISA. The data is presented as absolute differences in sTNFα secretion in the −237 homozygous versus heterozygous group. (c) Stimulation of TNFα production on a −237AA background was reduced relative to −237GG in the presence of different stimuli. The data is presented as absolute differences in soluble TNFα secretion (pg/ml) for a single −237GG and −237AA homozygous BCL line. Wilcoxon-Mann-Whitney tests were used for statistical comparisons, and two-tailed P values are indicated in (a) and (b).