Our study is the first to prospectively compare and validate different DNA sampling sources. Results show that plasma, serum, BEC, or DBS can be used as a source of DNA for IL28B genotyping, with full concordance (100% of sensitivity) with whole blood DNA extraction. The various extraction procedures gave identical SNP genotypes, which confirms that genomic DNA prepared from small amounts of serum or plasma can serve as a template to amplify DNA segments in order to detect genetic alterations, as described by Lin and Floros 
. Moreover, this study determined the minimal quantity of sera and plasma to be used (4 µL and 40 µL respectively) to reach the cut-off of sensitivity of detection.
It is important to recall that the stability and integrity of genomic DNA depend on storage conditions such as temperature, freeze-thaw cycles, and buffer composition. We observed no influence of storage conditions at ambient temperature, incidently showing postal delay in DNA sample shipping may be avoided. There was no difference in DNA from baseline to 12 days for the different sources of DNA tested (BEC, DBS, whole blood, and plasma). FTA cards, plasma, and sera are appropriate tools for clinical study because of their long term DNA conservation.
The combination of a micro-extraction procedure from serum and PCR genotyping provides a rapid and inexpensive tool for genetic analysis 
. A small amount of serum (250 µL) can be very informative, since it yields enough DNA to analyse several genetic markers. Note that plasma or serum is more reliable than whole blood for clinical studies, specifically for retrospective studies based on stored DNA and for shipment of sera in clinical trial analysis with centralised laboratories 
. The present study also evidenced the possibility of using DNA from serum and plasma to simulate serum or plasma utilization for DNA analysis of stored samples.
Cancer patients have a greater amount of circulating DNA than healthy subjects 
. It seems unlikely that tumoural DNA originates from the lysis of circulating cancer cells because the number of circulating cells usually found in plasma is not high enough to explain the large amount of DNA detected 
. Apoptosis has been proposed as the origin of circulating DNA, but this mechanism is thought to be lost by proliferating cells 
As an alternative to the usual venipuncture technique, several methods have been described that use DBS from finger-puncture or oral swabs collected on DNA-cards 
. Buccal mucosa cell sampling is almost completely non-invasive and painless, reducing compliance issues. Samples collected generate DNA usable after shipment through conventional mail 
. Sample collection does not require highly trained personnel or an established ‘cold chain’ to preserve samples until DNA is extracted. FTA™ cards are a viable storage matrix from DNA, and can be extracted to perform Genome Wide Analysis Studies analysis (GWAS) 
. Moreover, GWAS are commonly used to identify genetic predispositions of many human diseases. Large repositories of biological specimens for clinical and genetic investigations have been established to store material and data for these studies.
Another important issue is that, ideally, tissue sampling should be non-invasive and painless, especially for children and psychiatric groups. Preparation of DNA also needs to be rapid, reliable, and consistent. In any large-scale genetic association project, per-unit cost of DNA preparation becomes high. Also, DNA sample collection is needed in genotyping and in pharmacogenetic studies to understand the inter-individual variability of drug responses.
We also analysed patients' acceptability of the various sampling conditions. Buccal smear had an excellent and acceptability rate, the highest compared with serum and dried blood spot (data not shown).
In conclusion, we report that extracting genomic DNA from small amounts of serum, DBS, and BEC is an appropriate alternative to extracting DNA from peripheral blood cells and offers the possibility to analyse existing specimens. New patterns in genetic markers might be considered using serum as DNA source. DNA cards clearly facilitate genetic and pharmacogenetic testing for routine clinical practice. Moreover, collection and extraction of DNA from buccal smear are a noninvasive, convenient, and cost-effective alternative to blood sampling for participants and researchers, and can be mailed out for self-collection, overcoming geographical impediments. For patients with chronic hepatitis C infection, treatment response may be established through large screening for personalized medicine.