Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2)

Abstract

The possibility that four loci (REN, THO, PARP, SOD2) are associated with longevity was explored by comparing the genotypic pools of subjects older than 100 years with those of younger subjects matched for sex and geographic area (northern and southern Italy). The markers (all located within the respective gene) were HUMREN4; HUMTHO1; HUMPARP (gt)845nt; SOD2(C/T)401nt. In order to reduce the number of genotypes, multiallelic polymorphisms were recoded as diallelic according to allele size and frequency patterns (small: S, and large: L, alleles). A significant loss of LL homozygous genotypes was found at the THO locus in male but not in female centenarians with respect to matched controls. On the other hand no significant difference was found between case/control genotypic frequencies at REN, PARP, SOD2 loci. The latter loci therefore do not affect inter-individual variability in life expectancy (at least in terms of qualitative variants associated with the tested markers). However, the data is consistent with an association between the THO locus and longevity.

Association of TH01 with human longevity revisited

“…The frequency of the LL genotype was higher in German LLI than in controls, in contrast to the result in Italians. 1 In our sample, the distribution of the ungrouped allele and genotype frequencies in cases and younger controls was very similar (Figure 1). An overall comparison of allele or genotype frequencies showed no significant difference between the two groups (alleles: P¼0.48, genotypes: P¼0.71).…”

“…For a significance level of 0.05, our samples had a power of over 99 or 89%, respectively, to replicate the previous results observed for South Italian males and females. 1 Despite sufficient power, the association between TH01 and longevity was not replicated in the studied German samples (P values for comparison of LL versus SL/SS: 0.25 for males, 0.91 for females; Table 1). Furthermore, we repeated our analysis for the subgroup of centenarian male cases (the German female cases were all centenarians).…”

“…In a previous study, TH01 was reported to be associated with longevity in Italian men. 1 A statistically significant decrease in the frequency of long alleles (Z9) was observed in centenarians compared with younger males from the northern (26 centenarians versus 49 controls) and southern (27 centenarians versus 113 controls) parts of the country. This finding would indicate a potential survival disadvantage for LL carriers.…”

“…The primary aim of the study was to try to validate the result of De Benedictis et al 1 Secondary end points of the study were other potential differences in the TH01 allele distribution between cases and controls, with a special focus on allele 9.3. All P values were two-sided and were considered significant if smaller than 0.05.…”

“…A previous study investigated a possible association of the short tandem repeat (STR) polymorphism in intron 1 of TH01 (localization: 11p15.5-p15, motif: TCAT) with longevity in Italians. 1 The authors reported a statistically significant reduction in the frequency of homozygotes of long TH01 tetranucleotide repeats (Z9) in male centenarians compared with younger men. There was no association in females.…”