The functional VNTR of IGH enhancer HS1.2 associates with human longevity and interacts with TNFA promoter diplotype in a population of Central Italy |
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Authors: | Valerio Napolioni Eliseo Serone Valentina Iacoacci Francesco M. Carpi Vincenzo Giambra Domenico Frezza |
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Affiliation: | 1. Innovation Pole for Genomics, Genetics and Biology, Perugia, Italy;2. Department of Life, Health and Environmental Sciences, University of L''Aquila, L''Aquila, Italy;3. Department of Biology “E Calef”, University of Tor Vergata, Rome, Italy;4. Terry Fox Laboratory, British Columbia Cancer Research Centre, Vancouver, BC, Canada |
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Abstract: | The dysregulation of both immune and inflammatory responses occurring with aging is believed to substantially contribute to morbidity and mortality in humans. We have already reported the association of the functional Variable Number of Tandem Repeat (VNTR) at the Immunoglobulin heavy chain (IGH) enhancer HS1.2 with Immunoglobulin levels and with several autoimmune diseases. Herein we tested the association of the VNTR at the HS1.2 enhancer with human longevity, also evaluating the possible modulatory effect of TNFA promoter diplotype (rs361525/rs1800629). HS1.2 enhancer genotypes have been determined for 193 unrelated healthy individuals from Central Italy divided into two groups: Group 1 (18–84 yrs, mean age 56.8 ± 19.4) and Group 2 (85–100 yrs, mean age 93.0 ± 3.5). Homozygous subjects for *2 allele were significantly disadvantaged in reaching higher life-expectancy (OR = 0.457, p = 0.021). A significant interaction between TNFA promoter diplotype status, HS1.2 2/2 genotype and the two Groups was found (p = 0.014). Of note, TNFA − 308A allele seems to exert a protective effect in HS1.2 2/2 carriers. These results support the hypothesis of an important role of HS1.2 VNTR in the puzzle of the immune-system regulation, evidenced also by the potential interaction with TNFA. Moreover, the previous results showing the association of HS1.2 *2 allele with inflammatory phenomena are consistent with the hypothesis that this allele is a detrimental factor in reaching advanced age. |
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Keywords: | VNTR, Variable Number of Tandem Repeats IGH, Immunoglobulin Heavy Chain TNFA, Tumor Necrosis Factor Alpha Ig, Immunoglobulin NF-κB, Nuclear Factor of Kappa light polypeptide gene enhancer in B-cells 1 3&prime RR, 3&prime Regulatory Region HWE, Hardy&ndash Weinberg Equilibrium |
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