Genetic Variants of CD209 Associated with Kawasaki Disease Susceptibility

Background

Kawasaki disease (KD) is a systemic vasculitis with unknown etiology mainly affecting children in Asian countries. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN, CD209) in humans was showed to trigger an anti-inflammatory cascade and associated with KD susceptibility. This study was conducted to investigate the association between genetic polymorphisms of CD209 and the risk KD.

Methods

A total of 948 subjects (381 KD and 567 controls) were recruited. Nine tagging SNPs (rs8112310, rs4804800, rs11465421, rs1544766, rs4804801, rs2287886, rs735239, rs735240, rs4804804) were selected for TaqMan allelic discrimination assay. Clinical phenotypes, coronary artery lesions (CAL) and intravenous immunoglobulin (IVIG) treatment outcomes were collected for analysis.

Results

Significant associations were found between CD209 polymorphisms (rs4804800, rs2287886, rs735240) and the risk of KD. Haplotype analysis for CD209 polymorphisms showed that A/A/G haplotype (P = 0.0002, OR = 1.61) and G/A/G haplotype (P = 0.0365, OR = 1.52) had higher risk of KD as compared with G/G/A haplotype in rs2287886/rs735239/rs735240 pairwise allele analysis. There were no significant association in KD with regards to CAL formation and IVIG treatment responses.

Conclusion

CD209 polymorphisms were responsible for the susceptibility of KD, but not CAL formation and IVIG treatment responsiveness.     

Association between polymorphisms in OAS2 and CD209 genes and predisposition to chronic hepatitis C in Russian population

Chronic hepatitis C is a severe liver disease caused by positive-strand RNA virus. Previously, we reported an association between seven single nucleotide polymorphisms (SNPs) in four innate immunity genes (OAS2, OAS3, CD209, and TLR3) and human predisposition to tick-borne encephalitis, caused by a virus from the same Flaviviridae family, in a Russian population. Currently, genotype and allele frequencies for these SNPs were analyzed in 75 chronic hepatitis C patients and compared with the population control (269 Novosibirsk citizens). Data obtained suggest that the OAS2 rs1293762 and CD209 rs2287886 SNPs are associated with predisposition to chronic hepatitis C in Russian population.     

Association between CD209 -336A/G and -871A/G Polymorphisms and Susceptibility of Tuberculosis: A Meta-Analysis

Background

The association between CD209 promoter polymorphisms (-336A/G, -871A/G) and tuberculosis (TB) risk has been widely reported, but results of previous studies remain controversial and ambiguous. To assess the association between CD209 polymorphisms and TB risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, we identified outcome data from all articles estimating the association between CD209 polymorphisms and TB risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 14 studies with 3,610 cases and 3,539 controls were identified. There was no significant association between CD209 -336A/G polymorphism and TB risk (OR = 1.04, 95% CI = 0.91–1.19 for G vs. A; OR = 1.13, 95% CI = 0.84–1.53 for GG vs. AA; OR = 1.04, 95% CI = 0.87–1.24 for GG+AG vs. AA; OR = 1.11, 95% CI = 0.88–1.39 for GG vs. AG+AA). However, the significant association was revealed for Asians in GG vs. AA (OR = 2.48, 95% CI = 1.46–4.22, P = 0.0008) and GG vs. AG+AA (OR = 2.10, 95% CI = 1.33–3.32, P = 0.001). For the CD209 -871A/G polymorphism, lack of an association was also found (OR = 0.81, 95% CI = 0.70–0.95 for G vs. A; OR = 1.00, 95% CI = 0.52–1.93 for GG vs. AA; OR = 0.73, 95% CI = 0.60–0.89 for GG+AG vs. AA; OR = 1.09, 95% CI = 0.57–2.10 for GG vs. AG+AA).

Conclusion

The present meta-analysis suggested that CD209 promoter polymorphisms (-336A/G, -871A/G) were unlikely to substantially contribute to TB susceptibility. However, the GG genotype of CD209 -336A/G polymorphism might be a genetic risk factor that increases TB susceptibility for Asians in GG vs. AA and GG vs. AG+AA.     

Polymorphism of <Emphasis Type="Italic">CD209</Emphasis> and <Emphasis Type="Italic">TLR3</Emphasis> genes in populations of North Eurasia

The DC-SIGN (dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing non-integrin) and TLR3 (toll-like receptor 3) proteins are key effectors of the innate immunity and particularly play an important role in the organism’s antiviral defense as pattern-recognition receptors. Previously, we demonstrated that certain genotypes and alleles of single nucleotide polymorphisms (SNPs) rs2287886 (G/A) in the promoter region of the CD209 gene (encoding DC-SIGN) and rs3775291 (G/A, Leu412Phe) in the exon 4 of the TLR3 gene are associated with human predisposition to tick-borne encephalitis in the Russian population. In the present work, the distribution of genotype and allele frequencies for these SNPs was studied in seven populations of North Eurasia, including Caucasians (Russians and Germans (from Altai region)), Central Asian Mongoloids (Altaians, Khakass, Tuvinians, and Shorians), and Arctic Mongoloids (Chukchi). It was found that the CD209 gene rs2287886 SNP A/A genotype and A allele, as well as the TLR3 gene rs3775291 SNP G/G genotype and G allele (the frequencies of which in our previous studies were increased in tick-borne encephalitis patients as compared with the population control (Russian citizens of Novosibirsk)), are preserved with a high frequency in Central Asian Mongoloids (who for a long time regularly came in contact with tick-borne encephalitis virus in places of their habitation). We suggested that predisposition to tick-borne encephalitis in Central Asian Mongoloid populations can be predetermined by a different set of genes and their polymorphisms than in the Russian population.     

Association of the FCN2 Gene Single Nucleotide Polymorphisms with Susceptibility to Pulmonary Tuberculosis

Ficolin-2 (FCN2) is an innate immune pattern recognition molecule that can activate the complement pathway, opsonophagocytosis, and elimination of the pathogens. The present study aimed to investigate the association of the FCN2 gene single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (TB). A total of seven SNPs in exon 8 (+6359 C>T and +6424 G>T) and in the promoter region (-986 G>A, -602 G>A, -557 A>G, -64 A>C and -4 A>G) of the FCN2 gene were genotyped using the PCR amplification and DNA sequencing methods in the healthy controls group (n = 254) and the pulmonary TB group (n = 282). The correlation between SNPs and pulmonary TB was analyzed using the logistic regression method. The results showed that there were no significant differences in the distribution of allelic frequencies of seven SNPs between the pulmonary TB group and the healthy controls group. However, the frequency of the variant homozygous genotype (P = 0.037, -557 A>G; P = 0.038, -64 A>C; P = 0.024, +6424 G>T) in the TB group was significantly lower than the control group. After adjustment for age and gender, these variant homozygous genotypes were found to be recessive models in association with pulmonary TB. In addition, -64 A>C (P = 0.047) and +6424 G>T (P = 0.03) were found to be codominant models in association with pulmonary TB. There was strong linkage disequilibrium (r² > 0.80, P < 0.0001) between 7 SNPs except the -602 G>A site. Therefore, -557 A>G, -64 A>C and +6424 G>T SNPs of the FCN2 gene were correlated with pulmonary TB, and may be protective factors for TB. This study provides a novel idea for the prevention and control of TB transmission from a genetics perspective.     

Single Nucleotide Polymorphisms in IL17A and IL6 Are Associated with Decreased Risk for Pulmonary Tuberculosis in Southern Brazilian Population

In Mycobacterium tuberculosis (MTB) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with tuberculosis (TB) outcome. The aim of this study was to evaluate the association between previously reported SNPs IL2–330 T>G (rs2069762); IL4–590 C>T (rs2243250); IL6–174 G>C (rs1800795); IL10–592 A>C (rs1800872); IL10–1082 G>A (rs1800896); IL17A -692 C>T (rs8193036); IL17A -197 G>A (rs2275913); TNF -238 G>A (rs361525); TNF -308 G>A (rs1800629) and IFNG +874 T>A (rs2430561) and pulmonary TB (PTB) susceptibility. We conducted a case-control study in individuals from Southern Brazil who were recruited between February 2012 and October 2013 in a high incidence TB city. We performed a multiplex genotyping assay in 191 patients with PTB and 175 healthy subjects. Our results suggest a decreased risk for PTB development associated with the IL17A -197A allele (OR = 0.29; p = 0.04), AA genotype (OR = 0.12; p = 0.04) and A carrier (AG/AA) (OR = 0.29; p = 0.004) and IL6 -174C carrier (CC/CG) (OR = 0.46; p = 0.04). We could not properly analyze IL17A -692 C>T (rs8193036) and IFNG +874T>A due to genotypic inconsistencies and found no evidence of association for the IL2, IL4, IL10 and TNF polymorphisms and PTB. In conclusion, our results show a protective effect of IL17 and IL6 polymorphisms on PTB outcome in Southern Brazilian population.     

Association analysis of v-AKT murine thymoma viral oncogene homolog 1 (AKT1) polymorphisms and type 2 diabetes mellitus in the Korean population

V-AKT murine thymoma viral oncogene homolog 1 (AKT1) is an important downstream target of the insulin-signaling pathway and may be an important regulator of pancreatic beta cell growth. This study investigated the association of theAKT1 gene with susceptibility to type 2 diabetes mellitus and its related traits. By sequencing theAKT1 gene in 24 unrelated individuals, we iden-tified 32 genetic variations including 30 single nucleotide polymorphisms and 2 deletions. For the association analysis, we selected seven single nucleotide polymorphisms (rs10138227, ?726G>A; rs3730358, +12574C>T; rs2494737, +12656T>A; rs2498796, +15761T>C; rs2498799, +19087 A>G; rs2494732, +19789G>A; rs3803304, +19835G>C) based on minor allele frequency (>0.05) and linkage disequilibrium status. The study included 483 type 2 diabetes patients (206 men and 277 women with mean age 64±2.8 years and mean age at onset 56 ± 8.1 years) and 1,138 non-diabetic control subjects (516 men and 622 women with mean age 64 ±2.9 years). Two single nucleotide polymorphisms (rs2498796, +15761T>C and rs2494732, +19789G>A) were found to be associated with risk of type 2 diabetes mellitus, and showed an increased risk of type 2 diabetes mellitus in a recessive model (OR=1.343, 95% CI 1.021–1.765,p=0.035 and OR=1.534, 95% CI 1.058–2.225,p=0.024, respectively). These SNPs were also associated with diabetes-related traits such as levels of fasting blood glucose and hemoglobin A1c. In addition, type 2 diabetes mellitus patients who also have dyslipidemia or high blood pressure showed significant association with single nucleotide polymorphisms in AKT1 when compared with healthy controls. These results indicate that genetic variation in AKT1 influences the development of type 2 diabetes mellitus in the Korean population.     

Polymorphisms in 5��-flanking regions of genes encoding adiponectin, leptin, and resistin are not associated with obesity of Polish children and adolescents

Genes encoding adipokines are important functional candidates for development of obesity. In this study we screened for polymorphism 5??-flanking regions of the adiponectin (ADIPOQ), leptin (LEP) and resistin (RETN) genes in a cohort of Polish obese children and adolescents (n = 243) and a control group of non-obese adults (n = 100). Altogether 13 SNPs (single nucleotide polymorphisms) and 1 InDel (insertion/deletion polymorphism) were found. Among them five polymorphisms, localized in the LEP gene, turned out to be novel, but their distribution was insufficient for association studies. We found no consistent evidence for association between obesity and the SNPs demonstrating minor allele frequency (MAF) above 0.2 (ADIPOQ: ?11377C>G, LEP: ?2548C>T, 19A>G, RETN: ?1300G>A, ?1258C>T, ?420C>G). Comparison of polymorphisms distribution in patients and control group suggested association with ADIPOQ ?11377C>G (Pearson test P = 2.76 × 10^?11), however, we did not observe any effect of this polymorphism on BMI or relative BMI (RBMI) within obese patients (P = 0.41). We conclude that the tested SNPs are not useful markers of childhood and adolescence obesity in Polish population.     

A haplotype in the CCR5 gene promoter was associated with the susceptibility to HIV-1 infection in a northern Chinese population

It has been reported that single nucleotide polymorphisms (SNPs) in the promoter of the CCR5 gene are associated with the risk for HIV-1 infection and AIDS progression. Using resequencing, we performed a systematic survey of 78 HIV-1 seropositive individuals and 70 population-matched healthy control individuals from northern China to investigate SNPs of the CCR5 gene promoter and evaluated their effects on HIV-1 infection and the progression of AIDS. Linkage disequilibrium (LD) plots and haplotypes were generated using Haploview software. The association analyses were statistically compared using the Chi-square test with SPSS13.0 software for Windows. Seven SNPs (58755A>G, 58791C>T, 58934G>T, 59029A>G, 59353C>T, 59402A>G and 59653C>T) in the region of the CCR5 gene promoter were evaluated in this study. Among the seven SNPs, the minor allele frequencies of 58755G and 58791T were less than 2%. The differences in frequencies of the other five SNPs were not significant between case and control cohorts (P > 0.05). In the case cohort, the association between these SNPs and clinical features (CD4⁺ T-lymphocyte counts and clinical categories) was not significant (P > 0.05); however, there was a significant association between the haplotype GGTAC and susceptibility to HIV-1 infection (P < 0.05), which is not consistent with other reports studied in different populations. The results suggest that the haplotype GGTAC may have a role in the process of HIV-1 infection in the northern Chinese population.     

Association of the variants and haplotypes in the DOCK7, PCSK9 and GALNT2 genes and the risk of hyperlipidaemia

Little is known about the association between the single nucleotide polymorphisms (SNPs) and haplotypes of the dedicator of cytokinesis 7 (DOCK7), pro‐protein convertase subtilisin/kexin type 9 (PCSK9) and polypeptide N‐acetylgalactosaminyltransferase 2 (GALNT2) and serum lipid traits in the Chinese populations. This study was to determine the association between nine SNPs in the three genes and their haplotypes and hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG), and to identify the possible gene–gene interactions among these SNPs. Genotyping was performed in 733 HCH and 540 HTG participants. The haplotype of C‐C‐G‐C‐T‐G‐C‐C‐G [in the order of DOCK7 rs1168013 (G>C), rs10889332 (C>T); PCSK9 rs615563 (G>A), rs7552841 (C>T), rs11206517 (T>G); and GALNT2 rs1997947 (G>A), rs2760537 (C>T), rs4846913 (C>A) and rs11122316 (G>A) SNPs] was associated with increased risk of HCH and HTG. The haplotypes of C‐C‐G‐C‐T‐G‐C‐C‐A and G‐C‐G‐T‐T‐G‐T‐C‐G were associated with a reduced risk of HCH and HTG. The haplotypes of G‐C‐G‐C‐T‐G‐C‐C‐A and G‐C‐G‐C‐T‐G‐T‐C‐G were associated with increased risk of HCH. The haplotypes of C‐T‐G‐C‐T‐G‐C‐C‐G, G‐C‐A‐C‐T‐G‐C‐C‐G and G‐C‐G‐C‐T‐G‐C‐C‐A were associated with an increased risk of HTG. The haplotypes of G‐C‐G‐C‐T‐G‐T‐C‐A and G‐C‐G‐T‐T‐G‐T‐C‐G were associated with a reduced risk of HTG. In addition, possible inter‐locus interactions among the DOCK7, PCSK9 and GALNT2 SNPs were also noted. However, further functional studies of these genes are still required to clarify which SNPs are functional and how these genes actually affect the serum lipid levels.     

Polymorphism identification in goat GNRH1 and GDF9 genes and their association analysis with litter size

This study investigated the polymorphisms of GNRH1 and GDF9 genes in 641 goats of three breeds: Xinong Saanen, Guanzhong and Boer. Two allelic variants were identified in the GNRH1 gene (JN645280:g.3548A>G and JN645281:g.3699G>A) and one allelic variant was found in the GDF9 gene (JN655693:g.4093G>A). Furthermore, g.4093G>A was a missense mutation (p.Val397Ile of GDF9). Results of an association analysis indicated that SNPs g.3548A>G and g.4093G>A had significant effects on litter size (P < 0.05). The combination genotypes of SNPs g.3548A>G, g.3699G>A and g.4093G>A also affected litter size with the C₅ genotype having the highest litter size in the first, third, fourth and average parity. Hence, the biochemical and physiological functions, together with the results obtained in our investigation, suggest that the GNRH1 and GDF9 genes could serve as genetic markers for litter size in goat breeding.     

Cost-effective procedures for genotyping of human FCN2 gene single nucleotide polymorphisms

L-ficolin (ficolin-2) is a complement-activating pattern-recognition lectin taking part in the innate immune response. Both its serum concentration and sugar binding capacity are influenced by single nucleotide polymorphisms (SNP) of the corresponding FCN2 gene. Cost-effective and simple procedures, based on polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism for an investigation of four FCN2 SNPs are proposed: ?64 A?>?C (rs7865453), ?4 A?>?G (rs17514136; both located in the promoter region), +6359 C?>?T (rs17549193), +6424 G?>?T (rs7851696; both in exon 8). Variant alleles of ?64 and +6424 (in strong linkage disequlibrium) are known to be associated with low L-ficolin level or activity. In contrast, variant alleles at positions ?4 and +6359 (also in strong linkage disequlibrium) correspond to higher values. Since several L-ficolin clinical associations have been reported, FCN2 genotyping seems to be a valuable tool for disease association studies.     

Caspase8 rs1035142 G>T polymorphism was associated with an increased risk of esophageal cancer in a Chinese population

Esophageal cancer is one of the ten most common cancers in the world and has poor prognosis. Apoptosis is considered a fundamental component in cancer pathogenesis. We conducted a hospital-based case–control study to evaluate the genetic effects of 16 apoptosis associated single nucleotide polymorphisms (SNPs) on esophageal cancer development. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. Genotypes were determined using a custom-by-design 48-Plex SNPscan? Kit. The caspase8 (CASP8) rs1035142 G>T polymorphism was associated with increased risk of ESCC by heterozygote comparison, homozygote comparison, a dominant genetic model and a recessive genetic model. However, no significant association was detected between the other 15 SNPs and ESCC risk. Stratified analyses indicated a significantly increased risk of ESCC associated with CASP8 rs1035142 G>T polymorphism was evident among all subgroups. These findings indicated that the functional polymorphism CASP8 rs1035142 G>T might contribute to ESCC susceptibility.     

Sample-to-SNP kit: A reliable,easy and fast tool for the detection of HFE p.H63D and p.C282Y variations associated to hereditary hemochromatosis

Classical hereditary hemochromatosis involves the HFE-gene and diagnostic analysis of the DNA variants HFE p.C282Y (c.845G > A; rs1800562) and HFE p.H63D (c.187C > G; rs1799945). The affected protein alters the iron homeostasis resulting in iron overload in various tissues. The aim of this study was to validate the TaqMan-based Sample-to-SNP protocol for the analysis of the HFE-p.C282Y and p.H63D variants with regard to accuracy, usefulness and reproducibility compared to an existing SNP protocol. The Sample-to-SNP protocol uses an approach where the DNA template is made accessible from a cell lysate followed by TaqMan analysis. Besides the HFE-SNPs other eight SNPs were used as well. These SNPs were: Coagulation factor II-gene F2 c.20210G > A, Coagulation factor V-gene F5 p.R506Q (c.1517G > A; rs121917732), Mitochondria SNP: mt7028 G > A, Mitochondria SNP: mt12308 A > G, Proprotein convertase subtilisin/kexin type 9-gene PCSK9 p.R46L (c.137G > T), Plutathione S-transferase pi 1-gene GSTP1 p.I105V (c313A > G; rs1695), LXR g.-171 A > G, ZNF202 g.-118 G > T. In conclusion the Sample-to-SNP kit proved to be an accurate, reliable, robust, easy to use and rapid TaqMan-based SNP detection protocol, which could be quickly implemented in a routine diagnostic or research facility.     

No impact of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms on response to statin therapy in the Greek population

Interindividual variability exists in statin lipid-lowering response, partially attributed to genetic factors. Organic anion-transporting polypeptide 1B1 (OATP1B1) encoded by SLCO1B1 gene (solute carrier organic anion transporter family member 1B1) facilitates hepatic uptake of simvastatin and atorvastatin. SLCO1B1 polymorphisms are strongly associated with statin-induced myopathy whereas few studies have assessed their effect on statin differential response. In the present study, we analyzed the association of SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms with response to atorvastatin and simvastatin in 386 adults (201 atorvastatin-treated and 185 simvastatin-treated) with primary hypercholesterolemia, all of Greek origin. Total cholesterol and low-density lipoprotein cholesterol were measured at baseline and on 6 months of treatment. Genetic polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. A novel RFLP protocol was developed for the simultaneous identification of 388A>G and 411G>A polymorphisms. SLCO1B1 521T>C, 388A>G and 411G>A polymorphisms were not associated with lipid-lowering response to atorvastatin or simvastatin. No sex-gene or statin dose-gene interaction was observed on the effect of the analyzed SLCO1B1 polymorphisms in statin lipid lowering response in either statin-treated patient cohort. Further studies in different populations are required to draw firm conclusion on the potential association of SLCO1B1 polymorphisms with statin lipid-lowering response.     

The Adiponectin variants contribute to the genetic background of type 2 diabetes in Turkish population

Adiponectin, an adipose tissue specific protein encoded by the Adiponectin gene, modulates insulin sensitivity and plays an important role in regulating energy homeostasis. Many studies have shown that single nucleotide polymorphisms (SNPs) in the Adiponectin gene are associated with low plasma Adiponectin levels, insulin resistance and an increased risk of type 2 diabetes mellitus. The aim of the present study was to evaluate the contribution of the Adiponectin gene polymorphisms in genetic background of type 2 diabetes in a Turkish population. In total, 169 unrelated and non-obese diabetic patients and 119 age- and BMI-matched non-diabetic individuals with no family history of diabetes were enrolled in this study. We detected a significant association between type 2 diabetes and two SNPs: SNP − 11391G > A, which is located in the promoter region of the Adiponectin gene, and SNP + 276G > T, which is found in intron 2 of the gene (P < 0.05). The silence SNP G15G (+ 45T > G) in exon 1 and SNP + 349A > G in intron 2 also showed a weak association with type 2 diabetes (P = 0.06 and P = 0.07, respectively), while SNPs − 3971A > G in intron 1 and Y111H, R112C and H241P in exon 3 showed no association (P > 0.05). In conclusion, these findings suggest that Adiponectin gene polymorphisms might be effective on susceptibility for type 2 diabetes development which emerged from the interactions between multiple genes, variants and environmental factors.     

Oxidative Stress-Related Genes in Type 2 Diabetes: Association Analysis and Their Clinical Impact

Worldwide prevalence of diabetes mellitus motivates a number of association studies to be conducted throughout the world. Eleven polymorphisms from nine candidate genes in oxidative stress pathway have been analyzed in eastern Indian type 2 diabetic patients (n = 145) and healthy controls (n = 100). Different biochemical parameters were also analyzed for their association with the disease. Significant associations were observed for rs2070424 A>G SOD1 (OR 3.91, 95% CI 2.265–8.142, P < 0.001), rs854573 A>G PON1 (OR 3.415, 95% CI 2.116–5.512, P < 0.001), rs6954345 G>C PON2 (OR 3.208, 95% CI 2.071–4.969, P < 0.001), RAGE rs1800624 ?374 T>A (OR 3.58, 95% CI 2.218–5.766, P < 0.001), and NOS3 ?786 T>C (OR 3.75, 95% CI 2.225–6.666, P < 0.001). Haplotype containing two risk alleles of PON1 and PON2 genes was significantly associated with disease (OR 8.34, 95% CI 1.554–44.804, P < 0.002). Our results suggest that carriers of major and efficient alleles of oxidative stress genes are more likely to survive the comorbid complications and single copy of risk allele is sufficient for developing the disease.     

Polymorphism distribution of RYR1, PRKAG3, HFABP,MYF-5 and MC4R genes in crossbred pigs

This study was designed to screen the crossbred pigs for SNPs in five candidate genes, associated with pork quality traits and to differentiate their genotypes by PCR–RFLP. The results indicated that genotypes of crossbred pigs were NN (90%) and Nn (10%) for RYR1; RR (83%) and QR (17%) for PRKAG3; HH (98%), Hh (1%) and hh (1%) for HFABP; DD (99%) and CD (1%) for MYF-5; and AG (57%), GG (26%) and AA (17%) for MC4R SNPs, respectively. Allelic frequencies for five SNPs {RYR1 (1843C>T), PRKAG3 (c.599G>A), HFABP (c.1322C>T), MYF-5 (c.1205A>C) and MC4R (c.1426A>G)} were 0.95 and 0.05 (N/n), 0.08 and 0.92 (Q/R), 0.99 and 0.01 (H/h), 0.00 and 1.00 (C/D) and 0.45 and 0.55 (A/G), respectively. The effect of RYR1 (1843C>T) SNP was significant on pH₄₅ (P?<?0.05), pH₂₄ (P?<?0.05) and protein % (P?<?0.05). The PRKAG3 (c.599G>A) and MC4R (c.1426A>G) SNP had significant association with dressing percentages. The results revealed that RYR1, PRKAG3 and MC4R SNPs may be used in marker associated selection for pork quality traits in crossbred pigs.     

CD209 genetic polymorphism and tuberculosis disease

Background

Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa.

Methods and Findings

A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2x2 χ² = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77–0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson''s 2×2 χ² = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27–0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele.

Conclusion

This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response.