Association between macrophage migration inhibitory factor-173G/C polymorphism and psoriasis risk: A meta-analysis.

Background The association between macrophage migration inhibitory factor (MIF)-173G/C polymorphism and psoriasis risk has been reported in several studies with inconsistent conclusions. Aims This study aims to obtain a more convincing estimate of the relationship between the MIF-173G/C polymorphism and psoriasis risk. Methods Web of Science, EMBASE, PubMed, Wan Fang Database and Chinese National Knowledge Infrastructure (CNKI) were searched up to September 2021 and eligible studies were collected. The pooled odds ratios with 95% confidence intervals were calculated to estimate the effects of MIF-173G/C polymorphism on psoriasis risk under different genetic models. All analyses were conducted using the STATA12.0 software. Results A total of 1101 psoriasis cases and 1320 healthy controls from 6 relevant studies were included in this meta-analysis. Pooled analysis suggested that MIF-173G/C polymorphism was associated with increased psoriasis risk under the allelic model (C vs. G: odds ratio = 1.30, 95% confidence interval = 1.04-1.63, P = 0.020), heterozygous model (GC vs. GG: odds ratio = 1.53, 95% confidence interval = 1.05-2.22, P = 0.027) and dominant model (CC + GC vs. GG: odds ratio = 1.51, 95% confidence interval = 1.05-2.18, P = 0.027). Limitation Very few studies on the MIF-173G/C polymorphism in psoriasis have been reported till now, thus the number of studies included in the present meta-analysis was relatively small. Due to the number of studies being relatively small and the lack of raw data, stratified analysis by ethnicity or type of psoriasis was not carried out. Conclusion This meta-analysis demonstrated that MIF-173G/C polymorphism might be related to psoriasis risk. Carriers of the C allele and the GC genotype might have higher odds to present with psoriasis.

Single-nucleotide polymorphism and haplotype analysis of macrophage migration inhibitory factor gene and its correlation with serum macrophage migration inhibitory factor levels in North Indian psoriatic patients with moderate disease severity: A cross-sectional study.

BACKGROUND: Psoriasis is associated with significant morbidity and impaired quality of life. Identification of the host genes that influence disease susceptibility and can potentially guide future, targeted therapy is the need of the hour. AIMS: The aim of the study was to investigate the associations of macrophage migration inhibitory factor (MIF) gene polymorphisms, that is, a 5-8-CATT tetra nucleotide repeats at -794 (-794*CATT5-8) and a single-nucleotide polymorphism at -173 (-173*G/C) with the risk of chronic plaque psoriasis and to observe the correlation, if any, of disease determinants with genetic functional variants and circulating MIF levels. METHODS: Five hundred and seventeen individuals (265 psoriasis patients and 252 controls) were genotyped for MIF gene polymorphisms. Data were analyzed with respect to disease susceptibility, serum MIF levels, disease severity, age at onset, disease duration and presence of comorbidities. RESULTS: The presence of co-morbidities was more frequently noted in patients with late onset disease (P = 0.01). No statistically significant differences were observed either in genotype (P = 0.680) or allele frequency (P = 0.69) with respect to distribution of MIF-173*G/C polymorphism between patients and controls. The frequencies of genotypes -794*CATT 5/7 and 7/7 were significantly lower in patients (P = 0.027* and 0.038*, respectively). CATT*5/MIF-173*C haplotype occurred at a higher frequency in patients (odds ratio 3.03, 95% confidence intervals 1.09-8.47, P = 0.02). The mean serum MIF levels were significantly higher in patients as compared to controls (P < 0.001). The presence of either extended MIF -794*CATT repeats or C allele did not reveal any significant association with serum MIF levels or age at onset. Analysis of effect of various disease determinants revealed no significant association with genetic variants and serum MIF levels. LIMITATIONS: The lesional expression of MIF could not be studied. CONCLUSION: Our results showed that CATT*5/MIF-173*C haplotype is associated with increased susceptibility to psoriasis vulgaris.

Mapping leprosy-associated coding variants of interleukin genes by targeted sequencing.

Previous genotyping-based assays have identified non-coding variants of several interleukins (ILs) being associated with genetic susceptibility to leprosy. However, understanding of the involvement of coding variants within all IL family genes in leprosy was still limited. To obtain the full mutation spectrum of all ILs in leprosy, we performed a targeted deep sequencing of coding regions of 58 ILs genes in 798 leprosy patients (age 56.2 ± 14.4; female 31.5%) and 990 healthy controls (age 38.1 ± 14.0; female 44.3%) from Yunnan, Southwest China. mRNA expression alterations of ILs in leprosy skin lesions or in response to M. leprae treatment were estimated by using publicly available expression datasets. Two coding variants in IL27 (rs17855750, p.S59A, p = 4.02 × 10-8 , odds ratio [OR] = 1.748) and IL1RN (rs45507693, p.A106T, p = 1.45 × 10-5 , OR = 3.629) were significantly associated with leprosy risk. mRNA levels of IL27 and IL1RN were upregulated in whole blood cells after M. leprae stimulation. These data showed that IL27 and IL1RN are leprosy risk genes. Further functional study is required for characterizing the exact role of ILs in leprosy.

Lack of association of IL-10 (rs1800896) and IL-13 (rs1800925) with non-segmental vitiligo susceptibility in South Indian population.

BACKGROUND: Vitiligo is an autoimmune depigmentation disorder caused by multiple etiologies. Genetic polymorphisms in cytokine genes influence their expression and augment disease development. Analyzing the influence of genetic polymorphisms will help in better understanding of the complex etiopathogenesis of vitiligo. AIM: To study the influence of interleukin IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms on vitiligo risk in South Indian population. METHODS: Two hundred and sixty-four vitiligo patients and 264 controls were recruited in this study. Genotyping was done by quantitative PCR and plasma cytokine levels were measured by ELISA. RESULTS: Allele frequencies of IL-10 (rs1800896) and IL-13 (rs1800925) SNPs were observed to be equal in the groups. Mutant allele G of IL-10 (rs1800896) enhanced the familial inheritance of vitiligo (P < 0.0001, OR-25.1, 95% CI-7.64-82.7) and influenced the development of vulgaris type of vitiligo (P = 0.034, OR-1.83, 95% CI-1.07-3.13). Ancestral allele A of IL-10 (rs1800896) conferred protection against development of acrofacial vitiligo (P = 0.04, OR-0.56, 95% CI-0.33-0.95). Circulatory IL-10 levels in vitiligo patients were higher than controls (P < 0.0001). Individuals with genotype GG of IL-10 (rs1800896) had the highest circulatory levels of IL-10 (P < 0.0001). Among the genotypes of IL-13 (rs1800925) variant, none influenced the phenotype of nonsegmental vitiligo such as gender, family history, age of onset and types of vitiligo (P > 0.05). In addition, no difference was noted in the circulatory levels of IL-13 between patients and controls (P = 0.48). Within patients, CC genotype of IL-13 (rs1800925) was observed to enhance the circulatory IL-13 levels (P < 0.0001). LIMITATION: Replication group analysis in a larger multicentric cohort in future would validate further understanding of vitiligo susceptibility in South Indian ethnics. CONCLUSION: IL-10 (rs1800896) and IL-13 (rs1800925) polymorphisms did not confer risk to develop vitiligo in South Indian population.

A review of HLA allele and SNP associations with highly prevalent infectious diseases in human populations.

Human leucocyte antigen (HLA) alleles and single nucleotide polymorphisms (SNPs) lying in the HLA region are known to be associated with several infectious diseases among which acquired immunodeficiency syndrome, hepatitis B, hepatitis C, tuberculosis, leprosy and malaria are highly prevalent in many human populations worldwide. Distinct approaches such as case-control comparisons, immunogenetic analyses, bioinformatic peptide-binding predictions, ancient DNA and genome-wide association studies (GWAS) have contributed to improving this knowledge during the last decade, although many results still need stronger statistical and/or functional support. The present review updates the information regarding the main HLA allele and SNP associations observed to date for six of the most widespread and some other infectious diseases, and provides a synthetic illustration of these findings on a schematic HLA genomic map. It then discusses these results by stressing the importance of integrating information on HLA population diversity in disease-association studies.

Hepatitis B Virus Infection Among Leprosy Patients: A Case for Polymorphisms Compromising Activation of the Lectin Pathway and Complement Receptors.

Thousands of leprosy patients not only suffer from physical deformities, but also either have or have had hepatitis B virus (HBV) coinfection. Polymorphisms of the complement system modulate susceptibility to leprosy, but genetic susceptibility to past or present HBV infection is unknown. We used sequencing and multiplex sequence-specific PCR to genotype 72 polymorphisms of seven genes (MBL2, FCN1, FCN2, FCN3, MASP1, MASP2, C3) encoding components of the lectin pathway, and two genes encoding complement receptors (CR1, VSIG4) in 190 patients, of which 74 were positive for HBsAg and/or anti-HBc (HBV+, 93.2% with a resolved infection) and 116 lepromatous patients, and 408 HBV-blood donors. In addition, we tested for levels of proteins of the lectin pathway. We found no difference between serum concentrations of mannan-binding lectin (MBL), MBL-associated serine proteins (MASP-1, MASP-2, MASP-3, MAp44), ficolin-3 (FCN-3), soluble complement receptor 1 (sCR1) and MBL mediated C4 activation, measured by ELISA or TRIFMA in up to 167 HBV+ and HBV- patients. Haplotypes lowering protein levels or encoding dysfunctional proteins increased susceptibility to HBV infection: MBL2*LYQC (OR = 3.4, p = 0.02), MASP1*AC_CC (OR = 4.0, p = 0.015) and MASP2*1C2-l (OR = 5.4, p = 0.03). Conversely, FCN1*3C2 haplotype, associated with higher gene expression, was protective (OR = 0.56, P = 0.033). Other haplotypes associated with HBV susceptibility were: MASP2*2B1-i (OR = 19.25, P = 0.003), CR1*3A (OR = 2.65, P = 0.011) and VSIG4*TGGRCG (OR = 12.55, P = 0.014). Some polymorphisms in ficolin genes associated with lower protein levels increased susceptibility to leprosy/HBV infection: FCN*1 (OR = 1.66, P = 0.029), FCN2*GGGCAC (OR = 6.73, P = 0.008), and FCN3*del_del_C (OR = 12.54, P = 0.037), and to lepromatous disease/HBV infection: FCN2*TA (OR = 2.5, P = 0.009), whereas FCN2*MAG was associated with increased FCN-2 expression and resistance against coinfection (OR = 0.29, P = 0.026). These associations were independent of demographic factors and did not increase susceptibility to leprosy per se, except MASP2*1C2-l. Associations for FCN2, FCN3, MASP1, MASP2, and VSIG4 variants were also independent of each other. In conclusion, polymorphisms compromising activation of the lectin pathway of complement increase susceptibility to HBV infection, with ficolin polymorphisms playing a major role in modulating the susceptibility among leprosy patients.

Indonesians Human Leukocyte Antigen (HLA) Distributions and Correlations with Global Diseases.

In Human, Major Histocompatibility Complex known as Human Leukocyte Antigen (HLA). The HLA grouped into three subclasses regions: the class I region, the class II region, and the class III region. There are thousands of polymorphic HLAs, many of them are proven to have correlations with diseases. Indonesia consists of diverse ethnicity people and populations. It carries a unique genetic diversity between one and another geographical positions. This paper aims to extract Indonesians HLA allele data, mapping the data, and correlating them with global diseases. From the study, it is found that global diseases, like Crohn's disease, rheumatoid arthritis, Graves' disease, gelatin allergy, T1D, HIV, systemic lupus erythematosus, juvenile chronic arthritis, and Mycobacterial disease (tuberculosis and leprosy) suspected associated with the Indonesian HLA profiles.

Association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism with vitiligo susceptibility in Gujarat population.

BACKGROUND: Vitiligo is a multifactorial, polygenic, autoimmune skin disorder caused by selective destruction of melanocytes. Interleukin 1 receptor antagonist intron 2 polymorphism was found to be associated with various autoimmune disorders. AIMS: We aimed to investigate the association of interleukin 1 receptor antagonist intron 2 variable number of tandem repeats polymorphism (rs2234663) with vitiligo to assess interleukin 1 receptor antagonist transcript levels and to perform possible genotype-phenotype correlation. METHODS: Three hundred and seven vitiligo patients and 316 controls were enrolled in the study, genotyping of interleukin 1 receptor antagonist rs2234663 was performed by polymerase chain reaction, and relative gene expression of interleukin 1 receptor antagonist was carried out in peripheral blood mononuclear cells from patients (n = 36) and controls (n = 36) by real-time-PCR. RESULTS: A significant difference was observed in the frequency of interleukin 1 receptor antagonist *A (1/2) genotype among patients with active and stable vitiligo (P = 0.0172). Interleukin 1 receptor antagonist*A (2/2) genotype and allele frequencies were significantly different between SV patients and controls (P = 0.0246 and P = 0.0046, respectively). Significant difference was also observed for interleukin 1 receptor antagonist*A2 (allele) in active and stable vitiligo patients (P = 0.0060). However, other comparisons did not show any significant difference in genotype and allele frequencies. Moreover, interleukin 1 receptor antagonist*A (3/2) genotype was observed only in patients whereas interleukin 1 receptor antagonist*A (5/2) was observed only in controls. Gene expression analysis showed no significant difference in interleukin 1 receptor antagonist transcript levels in patients compared to controls (P = 0.5962). Interestingly, genotype-phenotype correlation analysis revealed that individuals with IL1RN*A (2/2) exhibited higher interleukin 1 receptor antagonist expression compared to other major genotypes interleukin 1 receptor antagonist*A (1/2) (P = 0.01) and interleukin 1 receptor antagonist*A (1/1) (P = 0.03). LIMITATIONS: More case-control studies on interleukin 1 receptor antagonist rs2234663 polymorphism and gene expression from different ethnic populations are required to explore the impact of interleukin 1 receptor antagonist in vitiligo susceptibility. CONCLUSION: Interleukin 1 receptor antagonist*A2 might be a risk factor for progressive vitiligo.

Genetic and molecular aspects of androgenetic alopecia.

Androgenetic alopecia is the most common form of progressive hair loss in humans. A genetic predisposition and hormonal status are considered as major risk factors for this condition. Several recent advances in molecular biology and genetics have increased our understanding of the mechanisms of hair loss in androgenetic alopecia. We review these advances and examine the trends in the genetic and molecular aspects of androgenetic alopecia.

A pleiotropic effect of the APOE gene: association of APOE polymorphisms with multibacillary leprosy in Han Chinese from Southwest China.

BACKGROUND: Patients with leprosy have a very low risk of Alzheimer disease (AD) and ß-amyloid (Aß) deposition is significantly lower in the brain tissue of elderly patients with leprosy compared with age-matched controls. Apolipoprotein E (ApoE) plays a critical role in lipid metabolic pathways and in the brain, facilitating the proteolytic clearance of Aß. We hypothesized that APOE confers risk of leprosy as lipid metabolism is involved in Mycobacterium leprae infection. OBJECTIVES: To investigate the potential genetic associations between APOE and leprosy in two independent Chinese case-control cohorts from the Yuxi and Wenshan prefectures, Yunnan Province of Southwest China. METHODS: Five APOE single-nucleotide polymorphisms (SNPs) were analysed in 1110 individuals (527 patients and 583 controls) from the Yuxi prefecture using a SNaPshot assay. Genetic variations in the entire APOE exons were screened in 1788 individuals (798 patients and 990 controls) from the Wenshan prefecture using next-generation sequencing technology. RESULTS: The AD-associated SNPs rs405509 and rs439401 increased the risk of leprosy per se and multibacillary leprosy (P < 0·005), but the APOE-ε4 allele did not. The SNPs rs405509 and rs439401 were cis expression quantitative trait loci (eQTL) for APOE expression in human skin. Differential APOE mRNA expression was observed in skin lesions of patients with type I reaction leprosy and those with multibacillary leprosy. APOE and related lipid genes are involved in an interaction network with leprosy susceptibility genes. CONCLUSIONS: The APOE gene is associated with leprosy, most likely by regulating lipid-metabolism-related genes.

Study of the relation between two common cyclooxygenase 2 gene polymorphisms with risk of developing and subtypes of vitiligo in Egyptian patients.

BACKGROUND/PURPOSE: Genetic factors play an important role in the pathogenesis of vitiligo. Cyclooxygenase 2 (COX2) gene induced by ultraviolet radiation controls the synthesis of prostaglandins, which are are found to be beneficial in treating vitiligo. COX2 gene polymorphism has been previously evaluated in Chinese population. We aimed to study the relation between two common COX2 gene polymorphisms with vitiligo and its subtypes amongEgyptian patients. PATIENTS AND METHODS: This study included 200 participants (100 vitiligo patients and 100 healthy controls). COX2-765G/C and -1195A/G gene polymorphism was studied by restriction fragment length polymorphism polymerase chain reaction analysis and the results were compared between the two groups and among different subtypes of vitiligo. RESULTS: Frequency of COX2-1195 AA, AG, GG genotypes showed no significant association among patients with vitiligo (P = 0.626, 0.321, 0.08, respectively); those with generalized vitiligo (P = 0.739, 0.291, 0.101, respectively) and those with segmental vitiligo (P = 0.410, 1.00, 0.676, respectively) compared to the control group. Regarding COX2-765G/C genotypes, GG genotype was more frequent among patients with vitiligo [84 (84%)] compared to controls [63 (63%)] (P = 0.001). GC genotype was significantly less frequent [15 (15%)] among patients compared to controls [32 (32%)] (P = 0.005). Generalized and segmental types of vitiligo also showed no significant difference in the frequency of COX2-765G/C genotypes compared with controls. LIMITATIONS: Being a pilot study, a relatively small number of participants were included. CONCLUSION: COX2-1195A/G gene polymorphism is not associated with the risk of developing vitiligo or with vitiligo subtypes. COX2-765 GG genotype is associated with vitiligo, especially of the generalized type.

Polymorphism of glutathione S-transferase M1 and T1 genes and susceptibility to psoriasis disease: A study from North India.

BACKGROUND: Increased oxidative stress and resulting inflammation has been emphasized as a factor in the pathogenesis of many diseases including psoriasis. Glutathione S-transferases (GSTs) protect against oxidative stress, inflammation, and genotoxicity. Polymorphisms in the GST genes may lead to an imbalance in pro- and antioxidant systems resulting in the increased production of reactive oxygen species that could influence the pathogenesis of psoriasis. AIM: The aim of this study was to investigate the association between GSTs (GSTM1 and GSTT1) gene polymorphism in patients with chronic plaque psoriasis as a factor in the susceptibility and development of psoriasis. MATERIALS AND METHODS: We assessed 128 patients with psoriasis and 250 age- and sex-matched healthy controls. Genomic DNA was extracted from peripheral blood by the phenol chloroform method. The null GSTT1 and GSTM1 genotypes were identified by multiplex polymerase chain reaction (PCR) method. RESULTS: The null genotype of GSTM1 and GSTT1 was seen in 45.3% and 40.6% in psoriasis patients whereas in the controls it was 34.4% and 20.0%, respectively. A significant association was seen between the null alleles of the GSTT1 (OR = 2.74) and GSTM1 (OR = 1.58) alone or in combination with tobacco use (P < 0.001) and psoriasis risk. The presence of both null genotypes of GSTM1 and GSTT1 further increased the risk of psoriasis (OR = 3.52) when compared with the positive genotypes of GSTM1 and GSTT1. LIMITATIONS: A major limitation of this study was the small sample size. A large epidemiological study is necessary to confirm these findings. CONCLUSIONS: The null genotype of GSTT1 is a strong predisposing factor for psoriasis in North India.

Vitamin D receptor expression and hepcidin levels in the protection or severity of leprosy: a systematic review.

Leprosy is a chronic infectious disease whose disequilibrium in the host's genetic, immunological and clinical mechanisms leads to distinct manifestations defining the type of immunological response. This review focuses its attention on the influence of the Vitamin D Receptor and hepcidin expressions that can suggest the protection or severity of leprosy.

Association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and susceptibility to vitiligo: Systematic review and meta-analysis.

BACKGROUND: Protein tyrosine phosphatase, non-receptor type 22 gene, which translates to lymphoid tyrosine phosphatase, is considered to be a susceptibility gene marker associated with several autoimmune diseases. Several studies have demonstrated the association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism with vitiligo. However, these studies showed conflicting results. Meta-analysis of the same was conducted earlier that included fewer number of publications in their study. AIM: We performed a meta-analysis of a total of seven studies consisting of 2094 cases and 3613 controls to evaluate the possible association of protein tyrosine phosphatase, non-receptor type 22 +1858C>T polymorphism with vitiligo susceptibility. METHODS: We conducted a literature search in PubMed, Google Scholar and Dogpile for all published paper on protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and vitiligo risk till June 2016. Data analysis was performed by RevMan 5.3 and comprehensive meta-analysis v3.0 software. RESULTS: Meta-analysis showed an overall significant association of protein tyrosine phosphatase, non- receptor type 22 +1858C→T polymorphism with vitiligo in all models (allelic model [T vs. C]: odds ratio = 1.50, 95% confidence interval [1.32-1.71], P< 0.001; dominant model [TT + CT vs. CC]: odds ratio = 1.61, 95% confidence interval [1.16-2.24], P = 0.004; recessive model [TT vs. CT + CC]: odds ratio = 4.82, 95% confidence interval [1.11-20.92], P = 0.04; homozygous model [TT vs. CC]: odds ratio = 5.34, 95% confidence interval [1.23-23.24], P = 0.03; co-dominant model [CT vs. CC]: odds ratio = 1.52, 95% confidence interval [1.09-2.13], P = 0.01). No publication bias was detected in the funnel plot study. LIMITATIONS: Limited ethnic-based studies, unable to satisfy data by gender or vitiligo-type are some limitations of the present meta-analysis. CONCLUSION: Stratifying data by ethnicity showed an association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T with vitiligo in European population (odds ratio = 1.53, 95% confidence interval [1.34-1.75], P< 0.001) but not in Asian population (odds ratio = 0.59, 95% confidence interval [0.26-1.32], P = 0.2). In conclusion, protein tyrosine phosphatase, non-receptor type 22 +1858 T allele predisposes European individuals to vitiligo.

Dense genotyping of immune-related loci implicates host responses to microbial exposure in Behçet's disease susceptibility.

We analyzed 1,900 Turkish Behçet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A-IL1B, IRF8, and CEBPB-PTPN1, with genome-wide significance (P < 5 × 10-8) by direct genotyping and ADO-EGR2 by imputation. We replicated the ADO-EGR2, IRF8, and CEBPB-PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO-EGR2 and IRF8, and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker at IL1A-IL1B, was associated with both decreased IL-1α and increased IL-1ß production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association (P = 5.89 × 10-15). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behçet's disease susceptibility.

Insights into metabolic disease from studying genetics in isolated populations: stories from Greece to Greenland.

Over the last 10 years substantial progress has been made in our understanding of the genetic basis for type 2 diabetes and related traits. These developments have been facilitated by technological advancements that have allowed comprehensive genome-wide assessments of the impact of common genetic variation on disease risk. Current efforts are now focused on extending this to genetic variants in the rare and low-frequency spectrum by capitalising on next-generation sequencing technologies. This review discusses the important contributions that studies in isolated populations are making to this effort for diabetes and metabolic disease, drawing on specific examples from populations in Greece and Greenland. This review summarises a presentation given at the 'Exciting news in genetics of diabetes' symposium at the 2015 annual meeting of the EASD, with topics presented by Eleftheria Zeggini and Torben Hansen, and an overview by the Session Chair, Anna Gloyn.

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample

Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

Association of the solute carrier family 11 member 1 gene polymorphisms with susceptibility to leprosy in a Brazilian sample.

Natural resistance-associated macrophage protein 1/solute carrier family 11 member 1 gene (Nramp1/Slc11a1) is a gene that controls the susceptibility of inbred mice to intracellular pathogens. Polymorphisms in the human Slc11a1/Nramp1 gene have been associated with host susceptibility to leprosy. This study has evaluated nine polymorphisms of the Slc11a1/Nramp1 gene [(GT)n, 274C/T, 469+14G/C, 577-18G/A, 823C/T, 1029 C/T, 1465-85G/A, 1703G/A, and 1729+55del4] in 86 leprosy patients (67 and 19 patients had the multibacillary and the paucibacillary clinical forms of the disease, respectively), and 239 healthy controls matched by age, gender, and ethnicity. The frequency of allele 2 of the (GT)n polymorphism was higher in leprosy patients [p = 0.04, odds ratio (OR) = 1.49], whereas the frequency of allele 3 was higher in the control group (p = 0.03; OR = 0.66). Patients carrying the 274T allele (p = 0.04; OR = 1.49) and TT homozygosis (p = 0.02; OR = 2.46), such as the 469+14C allele (p = 0.03; OR = 1.53) of the 274C/T and 469+14G/C polymorphisms, respectively, were more frequent in the leprosy group. The leprosy and control groups had similar frequency of the 577-18G/A, 823C/T, 1029C/T, 1465-85G/A, 1703G/A, and 1729+55del4 polymorphisms. The 274C/T polymorphism in exon 3 and the 469+14G/C polymorphism in intron 4 were associated with susceptibility to leprosy, while the allele 2 and 3 of the (GT)n polymorphism in the promoter region were associated with susceptibility and protection to leprosy, respectively.

The gene-immune-behavioral pathway: Gamma-interferon (IFN-γ) simultaneously coordinates susceptibility to infectious disease and harm avoidance behaviors.

Cytokine gene variants are known to influence both infectious disease susceptibility and harm-avoidant behaviors, suggesting that these risk variants may be pleiotropically linked to instinctual disease-avoidant traits. The gamma-interferon (IFNG) +874 T>A polymorphism (rs2430561) is an ideal candidate gene variant for immune-behavioral studies. It is a functional SNP, regulating IFNG mRNA expression; it is known to modulate serotonergic activity and is therefore capable of modifying behavior; and it has previously been associated with increased susceptibility to malaria, tuberculosis, leprosy and Chagas disease. We hypothesized that the infectious disease-high-risk IFNG +874 A-allele would be associated with four personality traits previously reported as behavioral defenses against infection: Harm Avoidance (HA), Extraversion (E), Exploratory Excitability (Exp E), and Openness to Experience (O). We tested this hypothesis in a sample of 168 healthy university students from Southern California genotyped for IFNG +874 T>A and evaluated by the Temperament and Character Inventory-Revised (TCI-R) and the NEO Five-Factor Inventory (NEO-FFI). We found that the infectious disease-high-risk IFNG +874 A-allele was associated with increased HA (P=0.001) and decreased E (P=0.030) and Exp E (P=0.030). These findings suggest that the IFNG +874 A gene variant is linked both to infectious disease susceptibility and to proactive behavioral defenses that reduce infection risk in healthy subjects.