found to be associated with longevity. This study aimed to investigate whether there was an association between the IL-6 2174 G/C promoter polymorphism and extreme longevity in a population of 81 centenarians compared with a control group of 122 middle-aged healthy subjects from Apulia, Southern Italy. The study found no evidence of an association between the IL-6 2174 G/C promoter allele and genotype frequencies in centenarians compared to controls. There was also no observed interaction with APOE alleles known to be linked to longevity. The study suggests that regional genetic differences in conjunction with differing environmental factors may explain previous results suggesting a role of this polymorphism in longevity.The text appears to be a scientific paper discussing the role of certain genetic polymorphisms in human longevity. Here is the processed text:

The APOE polymorphism has been extensively studied worldwide for its association with an increased risk of CAD and AD (Davignon et al., 1988; Saunders et al., 1993). Recent findings suggest a role of the APOE polymorphism in longevity (Schachter et al., 1994; Louhija et al., 1994; Panza et al., 1999). The first aim of this study was to investigate whether there was evidence in Southern Italy to support findings of an association between the IL-6 2174 G/C promoter polymorphism and extreme longevity. Secondly, we tested the possible interaction of APOE alleles with the IL-6 2174 G/C promoter polymorphism in view of our recent findings for reduced APOE 1 4 allele in centenarians (Panza et al., 1999).

2. Material and methods
2.1. Subject selection
A total of 203 subjects from Southern Italy were studied, including 81 centenarians and 122 middle-aged unrelated subjects or volunteers who presented themselves to the Department of Geriatrics, Bari University Hospital, Italy, between March 1995 and December 1998. The population of 81 centenarians was composed of 62 women and 19 men with a mean age of over 100 years. Centenarians were recruited from all over the Apulia region (regional distribution: 40% Bari region, 18% central, 4% northern, 5% eastern, 15% western, 18% southern) at their home through the Central Population Register of Apulia. They were all Caucasians residing in Southern Italy. The criteria for inclusion were to be at least 99 years old on the day of blood collection and no known diagnosis of dementia or other chronic neurological diseases or psychiatric syndromes with cognitive impairment (Solfrizzi et al., 1999), cerebrovascular disease, nephropathy or end-stage renal disease.

2.2. Genotyping
Genotyping was performed using the PCR method, followed by melting curve analysis. The IL-6 2174 G/C promoter genotype and allele frequencies were determined by allele counting. Statistical analysis was performed to make genotype and allele comparisons as well as test for agreement of data with Hardy-Weinberg principles.

2.3. Results
The frequencies of the different IL-6 2174 G/C promoter genotypes in our population were in Hardy-Weinberg equilibrium (centenarians: Pearson x2 = 0.41; df = 1; p = 0.52; middle-aged subjects: x2 = 0.54; df = 1; p = 0.36). No statistically significant differences were found in the IL-6 2174 G/C promoter genotype between centenarians and middle-aged subjects in our population. Similarly, the frequency of the IL-6*C allele (or vice versa IL-6*G allele) was comparable between centenarians and middle-aged control subjects. Finally, we did not find any statistically significant interaction among IL-6 2174 G/C promoter genotype, APOE alleles, and longevity.

3. Discussion
This study did not provide evidence to support the suggested role of the IL-6 2174 G/C promoter polymorphism in human longevity due to a decreased frequency of the IL-6*G/*G genotype in male centenarians compared with elderly and long-lived subjects in the only other study on centenarians (Bonafe` et al., 2001). However, high IL-6 concentrations were a credible predictor of increased disability and mortality in the elderly, and the IL-6*G/*G genotype was associated, probably through increased IL-6 plasma levels, with higher risk of AD, MID, and vascular diseases.

4. Conclusion
In conclusion, this study did not find evidence to support the suggested role of the IL-6 2174 G/C promoter polymorphism in human longevity. Further studies are needed to clarify the relationship between this polymorphism and IL-6 plasma levels.In 2001 and 2002, Rauramaa et al. found no effect of the IL-6 2174 G/C promoter polymorphism on baseline IL-6 plasma levels in 92 asymptomatic males. The conflicting findings reported could be linked to variability in the strength of association between the IL-6 2174 G/C promoter polymorphism and longevity, which could be modified by European regional differences in allele frequencies identified for both the APOE and angiotensin I converting enzyme 1 (ACE1) genes in centenarians (Panza et al., 1999, 2003). Interestingly, the IL-6*C allele frequency appears to vary across Europe, with an increasing trend from South to North in these very old populations: centenarians in the present study had a frequency of 29%, Italian centenarians had a frequency of 28.8% (Bonafe` et al., 2001), Irish octo/nonagenarians had a frequency of 45% (Rea et al., 2003), and Finnish nonagenarians had a frequency of 51% (Wang et al., 2001).