Association between dinucleotide repeat in non-coding region of interferon-gamma gene and susceptibility to, and severity of, rheumatoid arthritis

Khani-Hanjani, Abbas; Lacaille, Diane; Hoar, David I.; Chalmers, Andrew; Horsman, Douglas E.; Anderson, Michael J.; Balshaw, Robert; Pa, Keown

doi:10.1016/s0140-6736(00)02657-x

Cited by 96 publications

(51 citation statements)

References 31 publications

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“…[4][5][6][7] Although IFNg is known to play an important role in antiparasitic host defence as well as the pathogenesis of severe malaria, 11 we found no evidence of association between this microsatellite and susceptibility to severe malaria. However, this does not rule out an association between malaria and genetic determinants of IFNg production, as published studies of association between the microsatellite and IFNg production have been performed mainly in Caucasian individuals, 3 as were the data showing extremely strong correlation between the 12 CA-repeat allele and the IFNG þ 874T allele, which is located at a putative binding site for the transcription factor NF-kB.…”

Section: Investigation Of Malaria Susceptibility Determinantscontrasting

confidence: 65%

“…1,2 Several studies have reported associations between IFNG polymorphisms and susceptibility to disease. The first intron of the IFNG gene contains a highly polymorphic CA-repeat microsatellite, whose 12 CA-repeat allele is associated with high levels of IFNg production in vitro 3 and has been associated with resistance or susceptibility to various diseases including rheumatoid arthritis, 4 allograft fibrosis in lung transplant recipients, 5 acute graft-versus-host disease 6 and asthma. 7 This microsatellite allele has been associated with a singlenucleotide polymorphism (SNP) allele IFNG þ 874T, which coincides with a putative NF-kB binding site, 8 and has been associated with resistance to tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region

et al. 2005

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Interferon-gamma, encoded by IFNG, is a key immunological mediator that is believed to play both a protective and a pathological role in malaria. Here, we investigate the relationship between IFNG variation and susceptibility to malaria. We began by analysing West African and European haplotype structure and patterns of linkage disequilibrium across a 100 kb genomic region encompassing IFNG and its immediate neighbours IL22 and IL26. A large case-control study of severe malaria in a West Africa population identified several weak associations with individual single-nucleotide polymorphisms in the IFNG and IL22 genes, and defined two IL22 haplotypes that are, respectively, associated with resistance and susceptibility. These data provide a starting point for functional and genetic analysis of the IFNG genomic region in malaria and other infectious and inflammatory conditions affecting African populations.

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Section: Investigation Of Malaria Susceptibility Determinantscontrasting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region

et al. 2005

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“…Despite numerous data at the protein and cellular level implicating these cytokines in RA pathogenesis, genetic polymorphism analyses and their functional consequences have proven contradictory. [9][10][11][12][13] We have speculated that cytokine genes that regulate a Th1 dominant pathway may associate with RA. In particular, we have focused on the innate response cytokine interleukin (IL)-18.…”

Section: Introductionmentioning

confidence: 99%

Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

et al. 2005

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Interleukin (IL)-18 is an important mediator of innate and adaptive immunity. We searched for an association of IL-18 promoter single-nucleotide polymorphisms (SNP) with rheumatoid arthritis (RA) in Caucasians. The entire study population was composed of two independent cohorts from Germany (n ¼ 200) and Scotland (n ¼ 410). Presence of IL-18 SNP at positions À607 and À137 was determined by allele-specific PCR in 327 RA patients and 283 healthy donors (HD). Diplotype distributions of both loci were in Hardy-Weinberg equilibrium (HWE) in the German and Scottish HD cohorts. In contrast, locus À607 was in HW disequilibrium in German, and locus À137 in Scottish RA patients. Diplotypic exact w 2 tests suggested that À607CC was overrepresented in German, and À137CC in Scottish RA patients, but conservative w 2 trend analyses could not prove any significant disease association of these single loci. SNP À607 and À137 were in strong linkage disequilibrium. The À607C*À137C haplotype was more prevalent in German RA (3.2 vs 1.2%) and in Scottish RA patients (4.1 vs 0.9%) than in the respective HD cohorts. These observations suggest that SNP of both positions contribute to the genetic background of RA pathogenesis.

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“…The allele sizes were determined by the size of PCR products with ABI Prism s 3700 DNA Analyzer (Applied Biosystems) in comparison with GeneScan ROX-400 size standard using GeneScan software ( Figure 2). 13 The number of alleles and the distribution of these alleles in the Hong Kong Chinese population were determined in hypertensive subjects and normal controls. To confirm the number of nucleotide repeats, PCR products in a proportion of subjects were separated on 3.0% agarose gels, and the fragments were extracted from the gel by the QIAquick Gel Extraction kit (QIAGEN GmbH, Hilden, Germany) and sequenced.…”

Section: Introductionmentioning

confidence: 99%

Association of essential hypertension with a microsatellite marker on chromosome 17

et al. 2005

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Hypertension is related to sodium intake, and many patients with essential hypertension are overweight and have the metabolic syndrome. We therefore studied microsatellite markers close to the thiazide-sensitive Na-Cl cotransporter on chromosome 16 and a quantitative trait locus for abdominal obesity-metabolic syndrome (AOMS2) on chromosome 17, which have been found to be linked to hypertension in a previous genome scan in Chinese. There were 84 hypertensive subjects (44 men, 40 women, age 53713 years) and 88 normotensive controls (40 men, 48 women, age 54713 years) recruited. Specific oligonucleotide primers were used to amplify genomic DNA spanning the microsatellite markers D16S3396 and D17S1303 that consist of ATA and GATA repeats, respectively. We did not find any association between D16S3396 and blood pressure. In contrast, the distribution of D17S1303 genotypes differed between hypertensive subjects and normal controls (P ¼ 0.014). The number of GATA repeats correlated inversely with diastolic blood pressure (r ¼ À0.18, P ¼ 0.02) and body mass index (r ¼ À0.12, P ¼ 0.01). Nine GATA repeats in D17S1303 were associated with hypertension (OR 2.19, 95% CI 1.08-4.44, P ¼ 0.027), while 14 GATA repeats were associated with normotension (OR 0.26, 95% CI 0.10-0.66, P ¼ 0.002). The diastolic blood pressure in those with or without the (GATA)9 allele was 85.9713.6 and 79.2713.6 mmHg respectively (P ¼ 0.01), and in those with or without the (GATA)14 allele it was 73.8711.0 and 81.8714.0 mmHg respectively (P ¼ 0.003). Our results provide further evidence that a gene predisposing to hypertension in Chinese is in the vicinity of the microsatellite D17S1303.

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Association between dinucleotide repeat in non-coding region of interferon-gamma gene and susceptibility to, and severity of, rheumatoid arthritis

Cited by 96 publications

References 31 publications

Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region

Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region

Disease association of two distinct interleukin-18 promoter polymorphisms in Caucasian rheumatoid arthritis patients

Association of essential hypertension with a microsatellite marker on chromosome 17

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