Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study.

Background Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4-25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7-31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4-10.3. Limitations The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

Analysis of the rs2476601 polymorphism of PTPN22 in Mexican mestizo patients with leprosy.

Leprosy, a human chronic granulomatous disease caused by Mycobacterium leprae (M. leprae), remains endemic in certain countries despite the use of multidrug therapy. Recently, several host genes modulating the immune responses to M. leprae infection have been suggested to influence the acquisition and clinical course of leprosy. Lymphoid protein tyrosine phosphatase, encoded by the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, serves a negative regulatory role in T cell activation. The non-synonymous single-nucleotide polymorphism (SNP) rs2476601 (1858C>T) has been associated with autoimmune diseases. Here, the present study investigated if rs2476601 polymorphism was associated with leprosy in a Mexican mestizo population. Genotyping was performed in patients with leprosy (n=189) and control subjects (n=231) from regions with higher incidence of leprosy. Genotypic (P=0.44) and allelic frequencies (P=0.45) of the rs2476601 polymorphism were similar between patients and controls; genotypic frequencies were 91 vs. 94% for CC and 9 vs. 6% for CT, and the TT genotype was absent in both groups. Allelic frequencies were 96 vs. 97% for C, and 4 vs. 3% for T. In the same way, the genotypic (P=0.46) and allelic frequencies (P=0.47) from MB patients and controls were similar. In conclusion, there was a lack of association of the PTPN22 rs2476601 polymorphism with the development of leprosy, which suggests that this SNP was not a genetic risk factor for leprosy in the Mexican mestizo population studied.

HLA Alleles are Genetic Markers for Susceptibility and Resistance towards Leprosy in a Mexican Mestizo Population.

Despite the use of multidrug therapy, leprosy remains endemic in some countries. The association of several human leucocyte antigen (HLA) alleles and gene polymorphisms with leprosy has been demonstrated in many populations, but the major immune contributors associated to the spectrum of leprosy have not been defined yet. In this study, genotyping of HLA-A, -B, -DR, and -DQ alleles was performed in leprosy patients (n = 113) and control subjects (n = 117) from the region with the highest incidence for the disease in México. The odds of developing leprosy and lepromatous subtype were 2.12- and 2.74-fold higher in carriers of HLA-A*28, and 2.48- and 4.14-fold higher for leprosy and dimorphic subtype in carriers of DQB1*06. Interestingly, DQB1*07 was overrepresented in healthy individuals, compared to patients with leprosy (OR = 0.08) and the lepromatous subtype (OR = 0.06). These results suggest that HLA-A*28 is a marker for predisposition to leprosy and the lepromatous subtype and DQB1*06 to leprosy and the dimorphic subtype, while DQB1*07 might be a resistance marker in this Mestizo population.

Lack of Association of the Polymorphisms IL-17A (-197G/A) and IL-17F (+7488A/G) with Multibacillary Leprosy in Mexican Patients.

Background. Leprosy is a chronic infectious disease caused by the intracellular acid-fast bacilli Mycobacterium leprae; it has been determined that genetic factors of the host play an important role in the disease susceptibility. Thus, in this case-control study, we evaluated the possible association between the IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs and susceptibility to leprosy disease in Mexican population. Methods. Seventy-five leprosy patients and sixty-nine control subjects were included. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique. Results. We found nonsignificant differences in genotype and allele frequencies related to IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780) gene SNPs in MB as well as subclinical forms of leprosy disease versus healthy individuals. Conclusions. Since the sample size is not large enough, it is difficult to sustain an association of susceptibility to leprosy with genotypes or allele frequencies of IL-17A G-197A (rs227593) and IL-17F A7488G (His161Arg, rs763780), suggesting that IL-17 polymorphisms have no significant role in the genetic susceptibility to development of this disease in the Mexican Mestizo population.

Association of genetic polymorphism of HLA-DRB1 antigens with the susceptibility to lepromatous leprosy.

Despite the introduction of multidrug therapy and the overall reduction of leprosy prevalence in Mexico, the disease remains endemic in certain regions of the country. A genetic basis for the immune susceptibility to Mycobacterium leprae has already been established in different populations worldwide. In this study, we investigated the possible association of the HLA-DRB1 alleles with leprosy in a Mexican Mestizo population. The results demonstrated that the HLA-DRB1*01 allele is associated with lepromatous and dimorphic leprosy [P<0.001, odds ratio (OR)=4.6, 95% confidence interval (95% CI): 1.8-11.4; and P=0.03, OR=6.2, 95% CI: 1.1-31.6, respectively] and the frequency of the HLA-DRB1*08 allele was found to be significantly lower among leprosy patients compared to controls (P=0.046, OR=2.4, 95% CI: 1-5.8). In conclusion, although the association of the HLA-DR locus with leprosy has been established in different populations and several studies have demonstrated significant differences in the DR alleles, this study demonstrated an association of the HLA-DRB1*01 allele with susceptibility to lepromatous and dimorphic leprosy, as well as an association of the HLA-DRB1*08 allele with protection against leprosy in a Mexican Mestizo population.