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1.  TNFA-863 polymorphism is associated with a reduced risk of Chronic Obstructive Pulmonary Disease: A replication study 
BMC Medical Genetics  2011;12:132.
TNF-α mediated inflammation is thought to play a key role in the respiratory and systemic features of Chronic Obstructive Pulmonary Disease. The aim of the present study was to replicate and extend recent findings in Taiwanese and Caucasian populations of associations between COPD susceptibility and variants of the TNFA gene in a Spanish cohort.
The 3 reported SNPs were complemented with nine tag single nucleotide polymorphisms (SNP) of the TNFA and LTA genes and genotyped in 724 individuals (202 COPD patients, 90 smokers without COPD and 432 healthy controls). Pulmonary function parameters and serum inflammatory markers were also measured in COPD patients.
The TNFA rs1800630 (-863C/A) SNP was associated with a lower COPD susceptibility (ORadj = 0.50, 95% CI = 0.33-0.77, p = 0.001). The -863A allele was also associated with less severe forms of the disease (GOLD stages I and II) (ORadj = 0.303, 95%CI = 0.14-0.65, p = 0.014) and with lower scores of the BODE index (< 2) (ORadj = 0.40, 95%CI = 0.17-0.94, p = 0.037). Moreover, the -863A carrier genotype was associated with a better FEV1 percent predicted (p = 0.004) and a lower BODE index (p = 0.003) over a 2 yrs follow-up period. None of the TNFA or LTA gene variants correlated with the serum inflammatory markers in COPD patients (p > 0.05).
We replicated the previously reported association between the TNFA -863 SNP and COPD. TNFA -863A allele may confer a protective effect to the susceptibility to the disease in the Spanish population.
PMCID: PMC3209447  PMID: 21985478
2.  Bench-to-bedside review: Understanding genetic predisposition to sepsis 
Critical Care  2004;8(3):180-189.
Sepsis is a complex syndrome that develops when the initial, appropriate host response to an infection becomes amplified, and is then dysregulated. Among other factors, the innate immune system is of central importance to the early containment of infection. Death from infection is strongly heritable in human populations. Hence, genetic variations that disrupt innate immune sensing of infectious organisms could explain the ability of the immune system to respond to infection, the diversity of the clinical presentation of sepsis, the response to current medical treatment, and the genetic predisposition to infection in each individual patient. Such genetic variations may identify patients at high risk for the development of sepsis and organ dysfunction during severe infections. Single base variations, known as single nucleotide polymorphisms (SNPs), are the most commonly used variants. There has been great interest in exploring SNP in those genes involved in the inflammatory cascade resulting from the systemic inflammatory response to micro organisms. The rationale for studying gene SNPs in critical illnesses seeks to identify potential markers of susceptibility, severity, and clinical outcome; seeks to identify potential markers for responders and non-responders in clinical trials, and seeks to identify targets for therapeutic intervention. In this review, we focus on the current state of association studies of those genes governing the powerful bacterial infection-induced inflammation and provide guidelines for future studies describing disease associations with genetic variations based on current recommendations. We envision a time in the near future when genotyping will be include in the standard evaluation of critically ill patients and will help to prioritize a therapeutic option.
PMCID: PMC468916  PMID: 15153236
genetic susceptibility; haplotype; infection; inflammation; polymorphism
3.  Mitochondrial DNA transit between West Asia and North Africa inferred from U6 phylogeography 
BMC Genetics  2003;4:15.
World-wide phylogeographic distribution of human complete mitochondrial DNA sequences suggested a West Asian origin for the autochthonous North African lineage U6. We report here a more detailed analysis of this lineage, unraveling successive expansions that affected not only Africa but neighboring regions such as the Near East, the Iberian Peninsula and the Canary Islands.
Divergence times, geographic origin and expansions of the U6 mitochondrial DNA clade, have been deduced from the analysis of 14 complete U6 sequences, and 56 different haplotypes, characterized by hypervariable segment sequences and RFLPs.
The most probable origin of the proto-U6 lineage was the Near East. Around 30,000 years ago it spread to North Africa where it represents a signature of regional continuity. Subgroup U6a reflects the first African expansion from the Maghrib returning to the east in Paleolithic times. Derivative clade U6a1 signals a posterior movement from East Africa back to the Maghrib and the Near East. This migration coincides with the probable Afroasiatic linguistic expansion. U6b and U6c clades, restricted to West Africa, had more localized expansions. U6b probably reached the Iberian Peninsula during the Capsian diffusion in North Africa. Two autochthonous derivatives of these clades (U6b1 and U6c1) indicate the arrival of North African settlers to the Canarian Archipelago in prehistoric times, most probably due to the Saharan desiccation. The absence of these Canarian lineages nowadays in Africa suggests important demographic movements in the western area of this Continent.
PMCID: PMC270091  PMID: 14563219
4.  Major genomic mitochondrial lineages delineate early human expansions 
BMC Genetics  2001;2:13.
The phylogeographic distribution of human mitochondrial DNA variations allows a genetic approach to the study of modern Homo sapiens dispersals throughout the world from a female perspective. As a new contribution to this study we have phylogenetically analysed complete mitochondrial DNA(mtDNA) sequences from 42 human lineages, representing major clades with known geographic assignation.
We show the relative relationships among the 42 lineages and present more accurate temporal calibrations than have been previously possible to give new perspectives as how modern humans spread in the Old World.
The first detectable expansion occurred around 59,000–69,000 years ago from Africa, independently colonizing western Asia and India and, following this southern route, swiftly reaching east Asia. Within Africa, this expansion did not replace but mixed with older lineages detectable today only in Africa. Around 39,000–52,000 years ago, the western Asian branch spread radially, bringing Caucasians to North Africa and Europe, also reaching India, and expanding to north and east Asia. More recent migrations have entangled but not completely erased these primitive footprints of modern human expansions.
PMCID: PMC55343  PMID: 11553319

Results 1-4 (4)