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The protein expression level of the ADRB2 gene was measured by the ratio of light units of b2AR firefly to Renilla. Data represent mean ± SEM of four independent experiments performed in triplicate (more detailed description was in ‘Functional characterization of SNPs’ in Data S1, Supporting information).

Statistical analysis

Allele and genotype frequencies of SNPs were calculated and tested for departure from Hardy–Weinberg equilibrium using the chi-square test. Differences in allele and genotype distributions between case (long-lived population) and control (young population) were analyzed using logistic regression under various genetic models (Li et al., 2009). A Bonferroni method was used to correct multiple comparison in allele association

Linkage disequilibrium (LD) and haplotype blocks were constructed with genotyping data from this study and defined (r2 > 0.60) and visualized by the solid spine of LD method using Haploview 4.0 (http:// www.broadinstitute.org/scientific-community/science/programs/medical- and-population-genetics/haploview/haploview). The haplotypes with frequencies   5% were subjected to an association test with longevity. The permutation P-value was obtained by simulating 100 000 times for multiple comparison correction in haplotype association analysis (Rice et al., 2008).

The two-tailed P-values, odds ratios, and 95% confidence intervals (95% CI) are presented for all association tests. One-way ANOVA with post hocLSDtestwasusedtocompareBMI,systolicbloodpressure,anddiastolic blood pressure among three genotypes for each SNP, and to compare the ratios of firefly to Renilla luciferase (Ratio of Flu/Rlu) of three haplotypic groups. A P-value of < 0.05 was considered statistically significant.

Funding

This study was supported by grants from the National Basic Research Program of the Chinese Ministry of Science and Technology (973 Grant No.: 2007CB512100), Key Program from the National Natural Science Foundation of China NSFC (Grant No.: 30730047 and 70533010) and NIA/NIH (R01 AG023627).

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