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Common variants in SIRT1 and human longevity in a Chinese population.

Lin R, Yan D, Zhang Y, Liao X, Gong G, Hu J, Fu Y, Cai W - BMC Med. Genet. (2016)

Bottom Line: SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy.In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.e., rs12778366, rs3758391, rs3740051, rs33957861, rs7896005, rs12413112, rs11599176 and rs4746720) in the SIRT1 gene and human longevity.Current findings show that several common variants in SIRT1 are not associated with human longevity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Hainan Medical College, Haikou, 571199, Hainan, China.

ABSTRACT

Background: The silent information regulator SIR2/SIRT1gene has been demonstrated as regulating lifespan in many model organisms, including yeast, worms, fruit flies and rodents. SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy.

Methods: In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.e., rs12778366, rs3758391, rs3740051, rs33957861, rs7896005, rs12413112, rs11599176 and rs4746720) in the SIRT1 gene and human longevity.

Results: The 8 SNPs had strong linkage disequilibrium (LD) and were in an LD block, which was characterized by 4 common haplotypes that capture 99.3% of the genetic variation present within it. We found no evidence for statistically significant associations between the tested SIRT1 SNPs and longevity at the allele, genotype or haplotype levels.

Conclusions: Current findings show that several common variants in SIRT1 are not associated with human longevity.

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Related in: MedlinePlus

Pairwise linkage disequilibrium (LD) of the 8 SNPs in the SIRT1 gene under study. LD was measured by the D’ and r2statistics using the data from all subjects. The colors indicate the strength of pairwise LD. The darker color the higher the D’ or r2. a. D’ values b. r2 values Notes: For D’, a value of 100 reflects complete dependency between markers; For r2, a value of 100 reflects perfect dependency between markers. (SHEsis Software, ver. online)
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Fig1: Pairwise linkage disequilibrium (LD) of the 8 SNPs in the SIRT1 gene under study. LD was measured by the D’ and r2statistics using the data from all subjects. The colors indicate the strength of pairwise LD. The darker color the higher the D’ or r2. a. D’ values b. r2 values Notes: For D’, a value of 100 reflects complete dependency between markers; For r2, a value of 100 reflects perfect dependency between markers. (SHEsis Software, ver. online)

Mentions: No significant differences in genotype and allele distribution of the SNPs were observed between LLIs and younger controls (Table 2). All pairwise D’ values between the 8 SNPs were equal to or greater than 0.95 (Fig. 1a), which suggested that the 8 SNPs had strong LD and were in one block. Pairwise r2 values between SNP 1, 4, 6 and 7 (i.e., rs12778366, rs33957861, rs12413112 and rs11599176) were all greater than 0.95 (Fig. 1b), which indicated these 4 SNPs were almost in perfect LD. SNP 2 and 5 (i.e., rs3758391 and rs7896005) were also almost in perfect LD (D’ = 1, r2 = 0.99). Other pairwise r2 values were very low (all <0.25). As shown in Table 3, the eight SNPs constituted only four common haplotypes, which covered 99.3 % of the present Chinese population. None of the haplotypes differed significantly in frequency between the cases and the controls.Table 2


Common variants in SIRT1 and human longevity in a Chinese population.

Lin R, Yan D, Zhang Y, Liao X, Gong G, Hu J, Fu Y, Cai W - BMC Med. Genet. (2016)

Pairwise linkage disequilibrium (LD) of the 8 SNPs in the SIRT1 gene under study. LD was measured by the D’ and r2statistics using the data from all subjects. The colors indicate the strength of pairwise LD. The darker color the higher the D’ or r2. a. D’ values b. r2 values Notes: For D’, a value of 100 reflects complete dependency between markers; For r2, a value of 100 reflects perfect dependency between markers. (SHEsis Software, ver. online)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836161&req=5

Fig1: Pairwise linkage disequilibrium (LD) of the 8 SNPs in the SIRT1 gene under study. LD was measured by the D’ and r2statistics using the data from all subjects. The colors indicate the strength of pairwise LD. The darker color the higher the D’ or r2. a. D’ values b. r2 values Notes: For D’, a value of 100 reflects complete dependency between markers; For r2, a value of 100 reflects perfect dependency between markers. (SHEsis Software, ver. online)
Mentions: No significant differences in genotype and allele distribution of the SNPs were observed between LLIs and younger controls (Table 2). All pairwise D’ values between the 8 SNPs were equal to or greater than 0.95 (Fig. 1a), which suggested that the 8 SNPs had strong LD and were in one block. Pairwise r2 values between SNP 1, 4, 6 and 7 (i.e., rs12778366, rs33957861, rs12413112 and rs11599176) were all greater than 0.95 (Fig. 1b), which indicated these 4 SNPs were almost in perfect LD. SNP 2 and 5 (i.e., rs3758391 and rs7896005) were also almost in perfect LD (D’ = 1, r2 = 0.99). Other pairwise r2 values were very low (all <0.25). As shown in Table 3, the eight SNPs constituted only four common haplotypes, which covered 99.3 % of the present Chinese population. None of the haplotypes differed significantly in frequency between the cases and the controls.Table 2

Bottom Line: SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy.In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.e., rs12778366, rs3758391, rs3740051, rs33957861, rs7896005, rs12413112, rs11599176 and rs4746720) in the SIRT1 gene and human longevity.Current findings show that several common variants in SIRT1 are not associated with human longevity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Hainan Medical College, Haikou, 571199, Hainan, China.

ABSTRACT

Background: The silent information regulator SIR2/SIRT1gene has been demonstrated as regulating lifespan in many model organisms, including yeast, worms, fruit flies and rodents. SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy.

Methods: In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.e., rs12778366, rs3758391, rs3740051, rs33957861, rs7896005, rs12413112, rs11599176 and rs4746720) in the SIRT1 gene and human longevity.

Results: The 8 SNPs had strong linkage disequilibrium (LD) and were in an LD block, which was characterized by 4 common haplotypes that capture 99.3% of the genetic variation present within it. We found no evidence for statistically significant associations between the tested SIRT1 SNPs and longevity at the allele, genotype or haplotype levels.

Conclusions: Current findings show that several common variants in SIRT1 are not associated with human longevity.

Show MeSH
Related in: MedlinePlus