ABSTRACT
BACKGROUND: There has been recent recognition that the GSTM1 gene is associated with successful aging and longevity. It has been hypothesized that individuals with a GSTM1 deletion are at a greater risk for developing a plethora of diseases. This study was carried out to investigate the association between the rs574344 single nucleotide polymorphism, an expression quantitative trait locus of GSTM1, and longevity in the Han Chinese population. MATERIALS AND METHODS: We performed a case-control study that comprised 526 long-lived subjects (>97 years of age) and 783 younger subjects (aged 19-80 years) from the general population who served as controls. Identification of the genotypes of rs574344 was accomplished by combining polymerase chain reaction with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: The long-lived study population, when compared with the controls, showed a significantly higher frequency of the T/T genotype and the T allele of rs574344. We determined that the T/T genotype is associated with a longer lifespan (OR = 5.972, 95% CI 1.798-19.833, p = 0.001, for all genders; p = 0.006 adjusted by gender). We also observed a significant difference (p < 0.05) in the distribution of alleles and genotypes in both the male group (TT vs. TA, OR = 1.043, 95% CI 1.022-1.067, p = 0.043) and the female group (TT vs. TA, OR = 3.592, 95% CI 0.982-13.147, p = 0.039) Conclusion: We found significant associations between both the T allele and the T/T genotype of rs574344 with longevity in the Han Chinese population.
Subject(s)
Glutathione Transferase/genetics , Longevity/genetics , Adult , Aged , Aged, 80 and over , Alleles , Asian People/genetics , Case-Control Studies , China , Ethnicity/genetics , Female , Gene Frequency/genetics , Genetic Association Studies/methods , Humans , Male , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide/genetics , Quantitative Trait Loci/geneticsABSTRACT
Recent studies suggested that forkhead box class O3 (FOXO3) functions as a key regulator for the insulin/insulin-like growth factor-1signaling pathway that influence aging and longevity. This study aimed to comprehensively elucidate the association of common genetic variants in FOXO3 with human longevity in a Chinese population. Eighteen single-nucleotide polymorphisms (SNPs) in FOXO3 were successfully genotyped in 616 unrelated long-lived individuals and 846 younger controls. No nominally significant effects were found. However, when stratifying by gender, four SNPs (rs10499051, rs7762395, rs4946933 and rs3800230) previously reported to be associated with longevity and one novel SNP (rs4945815) showed significant association with male longevity (P-values: 0.007-0.032), but all SNPs were not associated with female longevity. Correspondingly, males carrying the G-G-T-G haplotype of rs10499051, rs7762395, rs4945815 and rs3800230 tended to have longer lifespan than those carrying the most common haplotype A-G-C-T (odds ratio = 2.36, 95% confidence interval = 1.20-4.63, P = 0.013). However, none of the associated SNPs and haplotype remained significant after Bonferroni correction. In conclusion, our findings revealed that the FOXO3 variants we tested in our population of Chinese men and women were associated with longevity in men only. None of these associations passed Bonferroni correction. Bonferroni correction is very stringent for association studies. We therefore believe the effects of these nominally significant variants on human longevity will be confirmed by future studies.
