C4A
Complement C4-A precursor (Acidic complement C4) (C3 and PZP-like alpha-2-macroglobulin domain-containing protein 2) [Contains: Complement C4 beta chain; Complement C4-A alpha chain; C4a anaphylatoxin; C4b-A; C4d-A; Complement C4 gamma chain] [CO4] [CPAMD2]
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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 C4 copy number or gene size (long C4L; short C4S) may influence the strength of the immune response and disease susceptibilities. Previously, an association between C4B copy number and life span was reported for Hungarians and Icelanders, where the C4B*Q0 genotype, which is defined by C4B gene deficiency, showed a decrease in frequency with age. Additionally, one of the studies indicated that a low C4B 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 C4 alleles in our large German longevity sample (∼ 700 cases; 94-110 years and ∼ 900 younger controls). No significant differences in the number of C4A, C4B and C4S were detected. Besides, the C4B*Q0 carrier state did not decrease with age, irrespective of smoking as an interacting variable. However, for C4L*Q0 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 C4L*Q0 carrier frequency in cases was visible (cases: 7.84%; controls: 10.00%).
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Alleles
- Complement C4
- DNA Copy Number Variations
- Female
- Gene Frequency
- Genotype
- Germany
- Humans
- Longevity
- Male
- Middle Aged
- Risk Factors
- Young Adult
The aim of this study was to examine the complement system and the distribution of some human leukocyte antigen (HLA) class III alleles (C4, BF) in healthy aged people (77 centenarians and 89 elderly subjects). We have also studied the alleles of C3, a complement component genetically unrelated to HLA, the immunochemical levels of C4 and C3 and serum functional hemolytic activity for classical (CH50) and alternative (AP50) complement pathway. The levels of C3 and C4 and the CH50 and AP50 were found to be within the normal range. The frequencies of C3, BF, and C4A alleles were similar in the cohorts that have been studied. For C4B null allele (C4BQ0) a trend toward an increase in the older cohort was observed, although the differences were not significant after statistical correction. Our data suggest that the complement system is well preserved in centenarians and elderly subjects and class III HLA antigens are equally distributed in aged cohorts and in young healthy individuals.
MeSH Terms
- Adult
- Aged
- Aged, 80 and over
- Aging
- Alleles
- Cohort Studies
- Complement Activation
- Complement C3
- Complement C4
- Complement Factor B
- Complement Pathway, Alternative
- Complement Pathway, Classical
- DNA
- Female
- Gene Deletion
- HLA Antigens
- Hemolysis
- Humans
- Male
- Middle Aged
- Polymorphism, Genetic