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In this study, we report for the first time HLA allele and haplotype frequencies in the modern Panamanian population at a two-field (four digits) resolution level. Reported frequencies were calculated from genotype data for the HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 loci of 462 healthy unrelated Panamanian adults of Hispanic ethnicity. In addition to providing new insights on the allelic structure of the Panamanian population and its origin, these data are critical for better planning of healthcare strategies in the country and for future research exploring the association with certain chronic and infectious diseases.

Amerindian Mapuche (Araucanians) are now living in Chile and Argentina at both sides of Andean Mountains. They are anthropologically and genetically different from southernmost South America Patagonian Amerindians. Most of the HLA alleles found in our Mapuche sample are frequent or very frequent in North and South America Amerindians: (1) Class I: A*02:01, A*03:01, A*68:01, B*39:09, B*51:01, (2) Class II: DRB1*03:01, DRB1*04:03, DRB1*07:01, DRB1*08:02, DRB1*14:02, DRB1*16:02. One of the nine most frequent extended haplotypes seems to be from European origin, suggesting the existence of a degree of admixture with Europeans in our Mapuche sample. It has been calculated of about 11 % admixture. Three of the extended haplotypes are also found in other Amerindians and five of them are newly found in Mapuche Amerindians: A*68:01-B*39:09-DRB1*08:02-DQB1*04:02; A*68:01-B*51:01-DRB1*04:03-DQB1*03:02; A*29:01-B*08:01-DRB1*03:01-DQB1*02:01; A*02:01-B*15:01-DRB1*04:03-DQB1*03:02; A*33:01-B*14:02-DRB1*07:01-DQB1*03:03. The medical importance of calculating HLA profile is discussed on the diagnostic (HLA and disease) and therapeutical bases of HLA pharmacogenomics and on the construction of a virtual transplantation HLA list profile. Also, anthropological conclusions are drawn.

Amerindians immigrated to Madrid (Spain) region are about 10% of the present day population. Amerindians are believed to be the first American inhabitants, before Na-Dene speakers, Aleuts and Eskimo. They may initially have arrived to America from Siberia and also from other parts of Pacific Sea (South Asia, Polynesia and Australia). Nowadays, they populate America from Canada to Tierra del Fuego (South America tip South). Most Amerindian immigrants to Madrid have come from Andean Countries in the last 10 years (mainly Ecuador, Bolivia, Peru and Colombia). They show an HLA profile with "quasi-specific alleles", which makes them different to the rest of the World. In the present work, we have aimed to determine the immigrants HLA profile in order to establish a virtual transplantation waiting list which may be useful for their therapeutic transplants, particularly bone marrow transplantation. This would be carried out together with Amerindian immigrants to other parts of Spain and with their own countries in order to build up transplantation programs. Specific epidemiology programs on HLA linked disease will also be established. Immigrant volunteer unrelated blood donors contributed to the present study. HLA typing was performed by standard methods and their HLA profile obtained and obtained and compared with 15,108 HLA chromosomes from the rest of the World, including Spaniards. The immigrants showed a typical Amerindian profile similar to isolated Amerindian ethnic groups and altogether different to other World inhabitants (including Spaniards). These are the first bases to set up transplantation and epidemiology studies in collaboration with their original population in America. Finally, the HLA profile found in these Amerindians does not indicate their American specific original area, as it is expected from previous studies, i.e.: they do not relate more with Andean than with other Amerindians in Neighbour Joining dendrograms or correspondence analyses.

HLA class I molecules are ligands for natural killer cells’ inhibitory (KIR DL) and activating (KIR DS) receptors. KIR DL receptors have a greater avidity for HLA class I molecules than KIR DS receptors. Thus, there is a possibility that HLA molecules drive KIR receptor selection. We have used the percentage of individuals bearing the genes KIR 3DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DL1, 2DL2, 2DL3, 2DL5 and 3DL1 in relatively well defined populations to test whether there is a different way of relating worldwide populations between KIR DS and KIR DL molecules. We h ave use d A RLEQUIN, D ISPAN and V ISTA computer p rograms t o c onstruct d endrograms a nd correspondence analyses showing the genetic relationships among different human world populations. Analyses based on KIR DS or KIR haplotype B ge nes show that populations are re lated according to geography, l ike a good a nthropological m arker (i .e.: HLA or Y chromosome systems). The results based on KIR DL or KIR haplotype A genes do not show such a correlation. Results are discussed taking into account the linkage of both HLA and KIR systems to microbial diseases and the possible evolutionary shaping of both HLA and KIR receptors repertoire by pathogens.

Aleuts HLA profile has been compared with that of neighboring and worldwide populations. Thirteen thousand one hundred and sixty-four chromosomes have been used for this study. Computer programs have obtained HLA allele frequencies, genetic distances between populations, NJ relatedness dendrograms, correspondence analysis and most frequent HLA extended haplotypes. Aleuts have inhabited Aleutian Islands since about 9000 years BP according to fossil and genetic (mtDNA) records. They are genetically different to Eskimo, Amerindian and Na-Dene speakers according to their HLA profile; this correlates with cultural and anthropological Aleut distinctiveness. No typical Amerindian HLA alleles have been found in a significant frequency. Their HLA relatedness to Saami (or Lapps, northern Scandinavians), Finns and Pomors (North-West Russia) indicates an ancient possible origin from the Baikal Lake Area (southern Siberia) around the present day Buryat peopling area; other origins are not discarded. Aleuts characteristic HLA profile may influence future transplantation programs in the region and be useful to study diseases linked to HLA epidemiology.

Human leukocyte antigen (HLA)-E is a nonclassical class I (Ib) gene with a restricted polymorphism. Only eight DNA alleles and three proteins of this gene have been described and their frequencies analyzed in Caucasian, Oriental, Asian Indian, and Negroid populations. In the present study, HLA-E polymorphism has been analyzed in six Amerindian and Mestizo populations from North and South America and compared with previously described populations. HLA-E*0101 is the most frequent allele found in all populations except in Afrocolombian and Wayu Amerindians, in which blood group analyses show a high admixture with Caucasian and African populations. Mazatecan and Mapuche (two Amerindian groups from North and South America, respectively) presented similar HLA-E frequencies, whereas Wayu Indians are more similar to the Afrocolombian population. The Mexican and Colombian Mestizo show similar allele frequencies to Amerindians with high frequencies of HLA-E*0101 and HLA-E*010302 alleles. Also, frequencies in Negroids and Asian Indians present a similar distribution of HLA-E alleles. These data are in agreement with worldwide restricted polymorphism of HLA-E because no new allele was detected in the six populations studied. The allelic frequencies show differences among Caucasian, Oriental, Mestizo and Indian populations. Ape major histocompatibility complex-E allelism is also very restricted: common chimpanzee (one allele); bonobo (two alleles); gorilla (two alleles); orangutan (one allele); rhesus monkey (eight alleles); cynomolgus monkey (two alleles); and green monkey (two alleles).

Caribbean Islands including Cuba were first inhabited by Meso-American and later by Arawak-speaking Amerindians from nowadays Venezuela. Spanish invaders brought to almost extinction to the Amerindian population after 1492. Black slaves from West Africa were taken into Cuba by Europeans. The degree of admixture among populations is approached. HLA alleles were studied by DNA techniques. Comparison with other worldwide populations (a total of 14.094 chromosomes) included genetic distances, Neighbour-Joining dendrograms, correspondence analyses and calculation of extended haplotypes. While African-European HLA features were clearly found, Amerindian HLA characteristics are less evident, indicating that Amerindian devastation was particularly marked after 1492 AD. However, typical Amerindian alleles have been found in our Cuban sample, i.e. DRB1*0403, DRB1*0404, DRB1*0407, DRB1*0411, DRB1*0802 and DRB1*1602. The presence of Amerindian alleles in Cubans [corrected] may have a bear in the making up of transplantation registries (both for bone marrow and solid organ transplantation) at the regional level and also be important for epidemiological studies of diseases linked to HLA.

The HLA allele frequency distribution of the Mexican Teenek Indians has been studied and compared with those of other First American Natives and worldwide populations (a total of 15694 chromosomes from 73 different populations were analyzed). This study corroborate the restricted HLA polymorphism in the Amerindian populations and demonstrate how the Amerindians show a relatively homogeneity as opposed to other First Native American groups. Finally, the present data support previous ones that state the lack of complete correlation between language and genetics in micro-environmental studies; Teenek Mayan language does not correspond with a close Mayan (Guatemala) relatedness.

A stem cell registry population from Hong Kong, of Chinese ethnicity, was examined for HLA-A and HLA-B alleles using a two-stage sequence-specific oligonucleotide probe system. Comparison of the HLA-A and HLA-B frequencies with different populations showed a close relationship with a Chinese population from Singapore, although there were several differences in the presence/absence of alleles at the HLA-B locus. Having the data available on these registry donors will influence the search strategy and the ongoing compilation of new donors to the registry. In addition, knowing which alleles do/do not occur in this population will aid in the distinction of ambiguities which result from the use of many of the typing kits available.

HLA-A, -B, -DRB1, -DQA1 and -DQB1 alleles have been studied in three relatively isolated populations of northern Spain from Cantabria ( Pas Valleys inhabitants or Pasiegos and Cabuernigos) and from the Basque Country (Arratia Valley inhabitants). These populations have been compared with neighbouring ones and other Mediterraneans by using neighbour-joining dendrograms and plane genetic distances.

The study of the MHC-G gene evolution during nearly 40 million years does not support a role for the full molecule. The MHC-G-like proteins of New World monkeys are probably classical presenting molecules. Old World Cercopithecinae monkeys do not have a full MHC-G molecule and human individuals homozygous for the HLA-G null allele are healthy and do not show birth pathologies.

HLA-G is a class Ib (nonclassical) major histocompatibility complex (MHC) protein expressed at the materno-fetal interface that may inhibit natural killer (NK) cell-mediated lysis in an allotype-independent manner. The human MHC-G transcript is differentially spliced, giving rise to at least six different forms. In order to study the evolutionary importance of this phenomenon, the presence of alternative splicing in MHC-G mRNA molecules from Pongidae (Chimpanzee, Gorilla, and Orangutan) has been investigated in the present work, and three alternative spliced isoforms (i.e.: G1, G2, and G3) have been found, but not the G4 and the soluble G5 and G6 ones. In addition, a novel MHC-G isoform is described in Gorilla, “G2 short.” This molecule is similar to the G2 isoform, but it lacks 29 amino acids normally encoded by exon 4. Our findings suggest that soluble isoforms are not necessary for MHC-G function(s) in Pongidae or that MHC-G is not a functional protein, because G1 is not necessary for survival in humans and Cercopithecinae bear stop codons in MHC-G exon 3.

HLA-G non classical class I locus shows a comparatively low polymorphism. It encodes for tolerogenic HLA molecules that may be important in autoimmunity and transplant (and foetal) rejection control. HLA-G molecules give negative signals to Natural Killer and T lymphocytes. In the present paper, a new allele, HLA-G*08, is described, which may be useful for monitoring transplants and for HLA and disease studies.

Aim The first heart transplant in Panama, made in March 2016, involved two hospitals, the Metropolitan Panama Complex and Punta Pacifica Hospital. The National Transplant Laboratory algorithm included all aspects of immunological compatibility in order to minimize one of the most common complications of transplantation: rejection such as acute heart donor. This paper presents the algorithm developed in the Laboratory in this first heart transplant. Methods The patient is female, 52 years old, blood type “A”. Molecular HLA typing use amplified DNA with specific HLA primer and hybridized with a panel of sequence specific oligonucleotide probes (SSOP) (LIFECODES HLA-SSO-Typing kits) The results of HLA recipient are: A ∗ 02, A ∗ 24, B ∗ 51, B ∗ 58, DRB1 ∗ 04, DRB1 ∗ 13, C ∗ 05, Cw ∗ 15, DQB1 ∗ 03(08), DQB1 ∗ 03(07), DPB1 ∗ 04, DPB1 ∗ 05. The studies to establish the presence of anti-HLA preformed antibodies included LIFECODES Antibody Screen, identification of anti-HLA Class I, II using LIFECODES Class I, II ID, and LIFECODES LSA Class I, II. The patient has in his serum anti-A ∗ 36,anti-B ∗ 14(B64) and anti DQB1 ∗ 02 with PRA Class I and Class II, 4%, 30%. The deceased donor was male, 24 years old, blood “A”, and HLA: A ∗ 02, A ∗ 24, B ∗ 58, B ∗ 63, DRB1 ∗ 13, DRB1 ∗ 13, Cw ∗ 07, C w ∗ 07, DQB1 ∗ 06, DQB ∗ 01. DPB1 01, DPB1 ∗ 02. The virtual Crossmatch was negative and actual crossmatching Test (DSA) was negative (LIFE CODES Donor Specific antibodies). In the Bank Laboratory we keep historical sera of the recipient and the pre-transplant serum and preserve HLA glycoproteins of the deceased donor for future humoral antibody-mediated rejection. Conclusion The time used by the laboratory to complete the algorithm was 4 h and the patient was successfully transplanted. Subsequent studies at 15, 30, 45 days have shown the absence of donor specific antibodies. The Laboratory has developed an algorithm that includes all high-tech procedures that avoid the risk of acute antibody-mediated rejection and guarantee further studies to monitor AMR presence. Final del formulario. Download high-res image (95KB) Download full-size image

America first inhabitants and peopling are still debated. In order to increase knowledge about these questions, we have aimed to detect HLA genes of an Amerindian secluded community: Jaidukama, who lives in North Colombia Equatorial forest. HLA genotyping and extended haplotype calculations were carried out in 39 healthy individuals belonging to 13 families. HLA frequencies were compared to other Amerindians and worldwide populations by calculating genetic distances, relatedness dendrograms and correspondence analyses. Only four DRB1 alleles were found (*0404, *0407, *1402 and *1602); however a total of 17 Amerindian different extended class I–class II HLA haplotypes were directly counted from the family studies, nine of them were specific of Jaidukamas. Some of the alleles or group of alleles within an extended haplotype (i.e. DQB1–DRB1) were also found in Asians and Pacific Islanders, further supporting existence of Asian and Pacific gene flow with Amerindians or a common founder effect. It is further supported that HLA extended haplotypes vary faster than alleles in populations. It is concluded that this unique model of Amerindian secluded families study suggests that rapid HLA haplotype variation may be more important than allele variation for survival (starting immune responses). This work may also be useful for future transplant programs in the area.

Summary Uros population from the Titikaka Lake live in about 42 floating reed (‘totora’) islands in front of Puno City (Peru) at a 4000 m high altiplano. They present both an mtDNA and a human leucocyte antigen (HLA) profile different from the surrounding populations: mtDNA A2 haplogroup is common to Uros and Amazon forest lowland Amerindians. HLA genetic distances between populations have been calculated and neighbour-joining dendrograms and correspondence analyses were carried out. Approximately 15 006 HLA chromosomes from worldwide populations have been used for comparisons. Only eight HLA-A alleles have been found, three of them accounting for most of the frequencies. The same phenomenon is seen for HLA-B, HLA-DRB1 and HLA-DQB1 alleles: a few alleles (3, 4 and 3, respectively) are present in most individuals. The presence of HLA-B*4801 and HLA-DRB1*0901 alleles in a relatively high frequency (although not the most frequent alleles found) is a characteristic shared with Asians and some populations from the Andean altiplano. Three specific Uros haplotypes have been found among the most frequent ones: HLA-A*680102-B*3505-DRB1*0403-DQB1*0302; HLA-A*2402-B*1504-DRB1*1402-DQB1*0301; and HLA-A*2402-B*4801-DRB1*0403-DQB1*0302. The present study suggests that Uros may have been one of the first populations from the shores of the Titikaka Lake coming from the Amazonian forest, which might have given rise to other later differentiated ethnic group (i.e. Aymaras). Uros HLA profile is also useful to study genetic epidemiology of diseases linked to HLA and to construct a future transplant waiting list by adding up regional lists in order to get a bigger pool for transplanting with better HLA matching.

The non-classical human leucocyte antigen (HLA) class I locus, HLA-G, shows a low protein polymorphism and a more varied DNA (eight proteins and 28 alleles). HLA-G DNA polymorphism accounts mainly for changes at third codon bases of the protein coding exons; this does not imply amino acid change in most cases. This relatively high HLA-G DNA polymorphism in comparison with their protein polymorphism suggests that evolutionary forces are acting upon HLA-G for invariance. This may be related to the immunotolerogenic function postulated for HLA-G.

HLA class I and class II alleles have been studied in 60 unrelated people belonging to Mayos ethnic group, which lives in the Mexican Pacific Sinaloa State. Mayos HLA profile was compared to other Amerindians and worldwide populations’ profile. A total of 14,896 chromosomes were used for comparisons. Genetic distances between populations, Neigbour-Joining dendrograms and correspondence analyses were performed to determine the genetic relationship among population. The new specific Mayo HLA haplotypes found are: HLA-A*02-B*35-DRB1*1406-DQB1*0301; HLA-A*02-B*48-DRB1*0404-DQB1*0302; HLA-A*24-B*51-DRB1*0407-DQB1*0302 and HLA-A*02-B*08-DRB1*0407-DQB1*0302. However, the typical Meso American HLADRB1*0407 represents a 40% of all DRB1 alleles. While common HLA characteristics are found in Amerindian distant ethnic groups, still new group specific HLA haplotypes are being found, suggesting that a common founder effect (i.e. high DRB1*0407) is noticed. Moreover, new HLA haplotypes are almost certainly appearing along time probably due to specific pathogen (?) selection for diversity. Mayo language is close to the Tarahumara one (another geographically close group); notwithstanding both groups are not genetically close according to our results, showing again the different evolution of genes and languages, which do not correlate. Finally, Sinaloa is one of the Mexican States in which more European genes are found. However, the results presented in this paper, where no European HLA genes are seen in Mayos, should have a bearing in establishing transplant programs and in HLA and disease studies.

We studied HLA class I and class II alleles in 191 Mexican families (381 non-related individuals) to directly obtain the HLA-A/B/DRB1/DQB1 haplotypes and their linkage disequilibrium (LD). The most frequent HLA haplotypes observed were: A*02-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*04-DQB1*0302, A*68-B*39-DRB1*04-DQB1*0302, A*02-B*35-DRB1*08-DQB1*04, A*33-B*1402-DRB1*01-DQB1*05, and A*24-B*35-DRB1*04-DQB1*0302. The four most common haplotypes found by our study involve those previously reported in Amerindian populations. LD analysis of HLA-A-B and HLA-B-DRB1 loci showed significant associations between A29(19)-B44(12), A33(19)-B65(14), A1-B8, A26(19)-B44(12), A24(9)-B61(40), B65(14)-DR1, B8-DR17(3), B44(12)-DR7, B7-DR15(2), and B39(16)-DR4. Also, all DRB1-DQB1 associations showed significant LD values. Admixture estimations using a trihybrid model showed that Mexicans from the State of Sinaloa (Northern Mexico) have a greater proportion of European genetic component compared with Mexicans from the Central area of Mexico, who have a greater percentage of Amerindian genes. Our results are important for future comparative genetic studies of different Mexican ethnic groups with special relevance to disease association and transplantation studies.

Six proteins, one null allele and 22 human leukocyte antigen (HLA)-G alleles were found in humans. Bonobo, chimpanzee and gorilla only show one allele and orangutan shows five alleles. All Cercopithecus alleles show stop codons at position 164 (Macaca mulatta with seven DNA alleles, Macaca fascicularis with seven DNA alleles and Cercopithecus aethiops with three DNA alleles). Cotton-top tamarin New World monkeys showed 20 DNA and protein alleles; the major histocompatibility complex (MHC)-G New World sequences seem to be closer to MHC-E and lack typical MHC-G primates intron 2-specific deletion. This seems to suggest that MHC-G genes in New World primates are not orthologous and that their function may be similar to that of classical presenting MHC genes.

The major histocompatibility complex (MHC)-F class Ib locus shows a limited polymorphism, and the function of its mainly intracellular protein is not clear. We have identified human leukocyte antigen (HLA)-F orthologous DNA sequences in Pongidae in order to study the MHC-F gene evolution and its products' function. HLA-F orthologous complementary DNA transcripts are found in chimpanzee and in the new primate species studied (bonobo, gorilla and orangutan). Analyses of the predicted amino acid sequences and their comparison with other primate MHC-F proteins show that MHC-F may be a protein with a typical class I structure and that the key residues of the peptide-binding region are highly conserved in MHC-F in all studied primates species. Thus, MHC-F conservation along the primate evolution suggests an important role in cellular physiology. It is possible that the MHC-F protein could be involved, together with MHC-G and MHC-E, in the natural killer cell activity regulation, although rhesus macaque cannot express complete surface MHC-G orthologue molecules.

We describe for the first time the high-resolution profiling of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand-mediated conformational analysis in this population were for class I: HLA-A*240201, *020101/09, *0206, *310102, *680102; HLA-B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA-Cw*0304, *0801, *0102, *040101; and for class II: HLA-DRB1*080201, *1402, *040701; HLA-DQB1*0402, *0301, *0302/07; HLA-DPB1*0402, *0401, *020102. In addition, a novel allele, HLA-A*0257, was found. Based on comparison of presently known HLA-DRB1 and -DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes.

The major histocompatibility complex (MHC)-F class Ib locus shows a limited polymorphism, and the function of its mainly intracellular protein is not clear. We have identified human leucocyte antigen (HLA)-F orthologous DNA sequences in Pongidae in order to study the MHC-F gene evolution and its products' function. HLA-F orthologous cDNA transcripts are found in chimpanzee and in the new primate species studied (bonobo, gorilla and orangutan). Analyses of the predicted amino acid sequences and their comparison with other primate MHC-F proteins show that MHC-F may be a protein with a typical class I structure and that the key residues of the peptide-binding region (PBR) are highly conserved in MHC-F in all studied primates species. Thus, MHC-F conservation along the primate evolution suggests an important role in cellular physiology. It is possible that the MHC-F protein could be involved, together with MHC-G and MHC-E, in the natural killer (NK) cell activity regulation, although rhesus macaque does not express MHC-G and MHC-E orthologues. The evolutionary pathway of the six-base-pair deletion at exon 2 existing in some primates is put forward.

Aymara Amerindians from the Titicaca Lake Andean highlands are studied for HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 gene frequencies. Genetic distances, neighbour-joining and correspondence analyses are performed by using other Amerindian and worldwide populations (15384 chromosomes are studied). The HLA genetic profile of Aymaras is different from neighbouring and language-related Quechuas (Incas). Both Quechuas and Aymaras seem to present an HLA-DRB1*0901 high frequency, which is present in a very low frequency or absent in Mesoamericans (Mazatecans, Mayans) and most studied Amerindians. Moreover, it is observed a closer relatedness of Aymaras with Amerindians from the Amazon Basin and Chaco lowlands, compared to Quechuans.

A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.

Aim Published reports have described KIR gene frequency distributions in more than 120 populations. Besides the classical HLA matching, KIR genes form an independent diverse immunogenetic system that implicated in influencing the clinical outcomes of allogeneic HSCT. KIRs are NK cell surface protein, and are encoded by the Leukocyte Receptor Complex (LCR) on chromosome 19 (19q13.4) and expressed on NK cell and subset of T cells. They play important role in the prevention of autoreactivity and elimination of viral-infected cells, tumor cells and anti-leukemia effect. The Aim of this study is to study the distribution of KIR gene polymorphisms in the Panamanian population for future consideration of incorporation in our Laboratory evaluation of donors as an additional selection criterion. Methods Stored genomic DNA (86 oC) of a total of 84 hematopoietic stem cell transplant (HSCT) donors evaluated between 2000-2012, from Instituto Oncologico, Hospital del Nino, Complejo Metropolitano of Panama, were tested for KIR genotyping using LIFECODES KIR TYPING KIT (Gen-Probe) and PCR-SSO. Results 22 patients (26%) were homozygous for haplotype A whereas 62 patients had at least one haplotype B (Bx, 74%). The most frequently seen KIR genotypes in Bx haplotypes in this cohort are: 3DL3, 2DL3, DL5, 2DS5, 2DP1, 2DL1, 3DP1, 2DL4, 3DL1, 3DS1, 2DS1, 2DS4, 3DL2 (13 patients, 15%); 3DL3, 2DS2; 2DL2, 2DL3, 2DL5, 2DS5, 2DP1, 2DL1, 3DP1, 2DL4, 3DL1, 3DS1, 2DS1, 2DS4, 3DL2 (6 patients, 7%); 3DL3, 2DS2, 2DL2, 2DL3, 2DL5, 2DS3, 2DP1, 2DL1, 3DP1, 2DL4, 3DL1 (6 patients, 7%). Conclusions This is the first report to describe KIR haplotypes and genotypes in the Panamanian population.

Background and Aims: It has been postulated that the HFE C282Y mutation (linked to human leukocyte antigen [HLA]-A3-B7 haplotype) is not only responsible for hereditary hemochromatosis; HLA class I alleles would also contribute to the disease pathogenesis. In addition, H63D mutation linked to HLA-A29-B44 would also be pathogenetic, particularly in the Mediterranean Basin and throughout the world. However, sporadic porphyria cutanea tarda (s-PCT) has also been linked to these HFE mutations. In the present work, we have studied HFE mutations and HLA genes to test these hypotheses. Methods: C282Y and H63D mutations together with HLA genetic typing have been performed in Spanish hereditary hemochromatosis (n = 98) and PCT (n = 63) patients. The etiologic fraction (δ) has been used to determine the absolute strongest gene linkage to both diseases. Results: The Spanish frequent HLA-A29-B44 haplotype is not significantly associated to the H63D mutations in hereditary hemochromatosis patients (although it is found more frequently in patients than in controls). Sporadic porphyria cutanea tarda patients do not show a significant association to H63D mutations, although it is also more frequent than in controls; however, compound H63D/C282Y subjects seem to bear a significant risk to s-PCT. Allelic C282Y (and not H63D) frequencies show a significant association with s-PCT. Conclusions: The postulated additional risk of hereditary hemochromatosis given by class I HLA antigens may be secondary to the HFE gene linkage disequilibrium with certain class I alleles or to the existence of other neighboring genetic pathogenetic factors in our Spanish sample.