in the CYP2C gene family showed a significant association with the longevity phenotype at the allele, genotype, or haplotype level in the examined German population. These results suggest that sequence variation in the CYP2C genes does not notably influence longevity in this population.

It is important to note that genetic parameters contribute significantly to adult lifespan, with around 30% of the variation attributable to genetic factors showing their strongest effect later in life. Long-lived individuals offer a unique opportunity to explore the genetic basis of healthy aging since they have avoided or survived age-associated diseases and have a favorable course of the aging process.

The CYP2C enzyme subfamily consists of four genes located next to each other on chromosome 10q and are mainly expressed in the liver but also in various other tissues. They modulate vascular homeostasis by metabolizing endogenous regulators of vascular tone and are involved in reducing ischemia-reperfusion injury in myocardial tissue. Some variants in these genes lead to markedly reduced or no enzyme activity, while others induce increased activity or expression. For example, variants CYP2C9*2 and 2C9*3 associated with reduced enzyme activity are clinically relevant for dose adjustment of the oral anticoagulant warfarin that is metabolized by CYP2C9.

In conclusion, while CYP2C enzymes play an important role in generating ROS and are susceptibility factors for age-related diseases, allelic variation in the CYP2C genes does not notably influence longevity in the examined German population.analysis, and metabolic activities. There are multiple errors in the original text, including misspelled words, incorrect verb tenses, and missing punctuation. Here is the processed text:

A statistically significant association with longevity was not found in either the whole sample or the centenarian subset. Statistical analyses were performed using c2 statistics and the open-source analysis toolset PLINK v.1.07 (http://pngu.mgh.harvard.edu/~purcell/plink/), with p-values less than .05 considered nominally statistically significant. Bonferroni correction for 56 tests was applied to the single-point results: Of the 56 tested markers, 28 were in strong linkage disequilibrium with each other (pairwise r2 > .8; calculated with the Haploview tagger pairwise option), so the number of markers considered for the Bonferroni correction could be reduced to 28. As two case-control analyses (whole sample and centenarians) were performed, a total of 56 tests need to be taken into account. The software program Haploview version 4.1 (http://www.broad.mit.edu/mpg/haploview/) was used to assess all polymorphisms for significant deviation from the Hardy-Weinberg equilibrium (HWE), calculate linkage disequilibrium (r2) between each marker pair, and conduct haplotype association analyses in blocks (31).

Candidate gene association studies have emerged as powerful tools in longevity research (32-37,39,48-55). So far, two longevity-relevant genes (APOE and FOXO3A) have been confirmed in many different populations. Because APOE and FOXO3A have been identified by candidate gene association studies, it seems that this method is still relevant for human longevity research, even in the era of genome-wide association studies. Although genome-wide association studies offer the advantage of detecting new longevity genes without a priori hypothesis, the power of hypothesis-driven candidate approaches is much higher than that of genome-wide association studies where millions of SNPs are tested, and multiple comparisons have to be taken into consideration as an essential part of determining statistical significance. Hence, so far, it has been difficult to detect new longevity variants by genome-wide studies, and apart from the APOE locus, none of the reported genome-wide association studies signals achieved conventional levels of statistical significance.

The whole sample of 1,384 German LLI, a subset of 616 centenarians, and a control group of 945 younger individuals were subjected to a gender-matched case-control analysis of 56 SNPs located in the CYP2C genes (CYP2C8, CYP2C9, CYP2C18, and CYP2C19). All SNPs were found to be in HWE (p > .001). Only one nominally significant association signal (rs11188059; p = .04) was observed in the analysis CCA of the centenarian sample (Table 1) that did not pass correction for multiple testing (Bonferroni-adjusted p = 1, assuming 56 tests; see Participants and Methods and Statistical Analysis). In the entire longevity sample (1,384 LLI and 945 controls), none of the tested SNPs showed a significant association.

With the applied approach, we likely captured all common variation present in the analyzed samples for the CYP2C gene region. Acknowledging that the selected markers might be insufficient to tag the genetic variation comprehensively, we cannot rule out the presence of rare polymorphisms that could influence longevity. However, with consideration of haplotype differences, if present...