Global Journal of Science Frontier Research, G: Bio-Tech & Genetics, Volume 22 Issue 2

2004] In a large meta-analysis involving 75 case-control studies with 18,727 cases and 17,102 controls [Yazdanyar S., 2009], individuals carrying this variant had an increased overall risk of Crohn's disease (OR = 2.2, 95% CI 2.0-2.5). (Table 2). Table 2: Auto inflammation candidate genes in juvenile idiopathic arthritis Gene Variant Zygosity Variantclassification NOD2 c.2104C>T (p.Arg702Trp) heterozygous IncreasedRiskAllele ADA2 c.145C>T (p.Arg49Trp) heterozygous UncertainSignificance NLRP12 c.1343G>C (p.Gly448Ala) heterozygous UncertainSignificance PSTPIP1 c.806T>A (p.Ile269Asn) heterozygous UncertainSignificance MEFV c.1341G>C (p.Lys447Asn) heterozygous UncertainSignificance When all three NOD2 genotypes were combined (p.Arg702Trp, p.Gly908Arg, and p.Leu1007Profs*2), the odds ratios for Crohn's disease were 2.4 (95% CI, 2.0- 2.8) for simple heterozygotes, 9.0 (95% CI 6.0-13.5) for compound heterozygotes, and 6.7 (95% CI 4.1-10.9) for homozygotes, compared with noncarriers. This variant is also referred to as R675W and SNP8 in the literature. ClinVar contains an entry for this variant (Variation ID: 4693). Experimental studies have shown that this missense change results in decreased NFkB activity and decreased response to lipopolysaccharide, muramyl dipeptide, and peptidoglycan compared to wildtype protein [Bonen DK., 2003; Li J, Moran T., 2004; Stevens C, 2013]. In summary, this is a frequently observed variant that is associated with approximately a 2.2-fold increased risk of Crohn's disease in population studies. Therefore, it has been classified as an Increased Risk Allele. and one mutation in 4 patients – in genes NLRP12 [c.1343G>C (p.Gly448Ala)]. This sequence change replaces glycine with alanine at cod on 448 of the NLRP12 protein (p.Gly448Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is present in population databases (rs104895566, ExAC 0.01%). This variant has been reported in an individual affected with chronic NLRP12- autoinflammatory disorder [Vitale A., 2013]. ClinVar contains an entry for this variant (Variation ID: 97886). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; AlignGVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance, MEFV [c.1341G>C (p.Lys447Asn)]. This sequence change replaces lysine with asparagine at codon 447 of the MEFV protein (p.Lys447Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs756322372, ExAC 0.003%). This variant has not been reported in the literature in individuals with MEFV-related conditions. ClinVar contains an entry for this variant (Variation ID: 279849). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance, ADA2 [c.145C>T (p.Arg49Trp)] This sequence change replaces arginine with tryptophan at codon 49 of the ADA2 protein (p.Arg49Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in an individual affected with Behçet's disease [Burillo-Sanz S., 2017]. ClinVar contains an entry for this variant (Variation ID: 375246). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. and PSTPIP1 [c.806T>A (p.Ile269Asn)] This sequence change replaces isoleucine with asparagine at codon 269 of the PSTPIP1 protein (p.Ile269Asn). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and asparagine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with PSTPIP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; 1 Year 2022 87 © 2022 Global Journals Global Journal of Science Frontier Research Volume XXII Issue ersion I VII ( G ) Autoinflammation Candidate Genes in Juvenile Idiopathic Arthritis