Investigation of Complement Component <i>C4</i> Copy Number Variation in Human Longevity

<div><p>Genetic factors have been estimated to account for about 25% of the variation in an adult's life span. The complement component C4 with the isotypes C4A and C4B is an effector protein of the immune system, and differences in the overall <i>C4</i> copy number or gene size (long <i>C4L</i>; short <i>C4S</i>) may influence the strength of the immune response and disease susceptibilities. Previously, an association between <i>C4B</i> copy number and life span was reported for Hungarians and Icelanders, where the <i>C4B*Q0</i> genotype, which is defined by <i>C4B</i> gene deficiency, showed a decrease in frequency with age. Additionally, one of the studies indicated that a low <i>C4B</i> copy number might be a genetic trait that is manifested only in the presence of the environmental risk factor “smoking”. These observations prompted us to investigate the role of the <i>C4</i> alleles in our large German longevity sample (∼700 cases; 94–110 years and ∼900 younger controls). No significant differences in the number of <i>C4A</i>, <i>C4B</i> and <i>C4S</i> were detected. Besides, the <i>C4B*Q0</i> carrier state did not decrease with age, irrespective of smoking as an interacting variable. However, for <i>C4L*Q0</i> a significantly different carrier frequency was observed in the cases compared with controls (cases: 5.08%; controls: 9.12%; p = 0.003). In a replication sample of 714 German cases (91–108 years) and 890 controls this result was not replicated (p = 0.14) although a similar trend of decreased <i>C4L*Q0</i> carrier frequency in cases was visible (cases: 7.84%; controls: 10.00%).</p>