Influence of protein tyrosine phosphatase gene (<scp>PTPN22</scp>) polymorphisms on rheumatic heart disease susceptibility in North Indian population

Gupta, Urvashi; Mir, Snober S.; Chauhan, Tanya; Garg, Naveen; Agarwal, Sarita; Pande, Shantanu; Mittal, Balraj

doi:10.1111/tan.12440

Cited by 7 publications

(7 citation statements)

References 25 publications

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“…The pooled concordance risk for ARF was 44% in monozygotic twins and 12% in dizygotic twins (OR 6.39, p<0.001), with an estimated heritability of 60%. To date, targeted genomic investigations have examined select genes involved in immune regulation including human leukocyte antigens (HLA), transforming growth factor-beta1, toll-like receptor 5, angiotensin I-converting enzyme gene, PTPN22, and signal transducers and activators of transcription (STATs) gene polymorphisms [ 17 – 23 ]. The most robust data comes from studies of the major histocompatibility complex human leukocyte antigens [ 3 , 24 ], with many finding polymorphisms within the HLA-DR locus, including a study from Uganda [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case

et al. 2016

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BackgroundEchocardiographic screening for detection of latent RHD has shown potential as a strategy to decrease the burden of disease. However, further research is needed to determine optimal implementation strategies. RHD results from a complex interplay between environment and host susceptibility. Family members share both and relatives of children with latent RHD may represent a high-risk group. The objective of this study was to use echocardiographic family screening to determine the relative risk of RHD among first-degree relatives of children with latent RHD compared to the risk in first-degree relatives of healthy peers.Methodology/Principal FindingsPrevious school-based screening data were used to identify RHD positive children and RHD negative peers. All first-degree relatives ≥ 5 years were invited for echocardiography screening (2012 World Heart Federation Criteria). Sixty RHD positive cases (30 borderline/30 definite RHD) and 67 RHD negative cases were recruited. A total of 455/667 (68%) family members were screened. Definite RHD was more common in childhood siblings of RHD positive compared to RHD negative (p = 0.05). Children with any RHD were 4.5 times as likely to have a sibling with definite RHD, a risk that increased to 5.6 times when considering only cases with definite RHD. Mothers of RHD positive and RHD negative cases had an unexpectedly high rate of latent RHD (9.3%).Conclusions/SignificanceSiblings of RHD positive cases with RHD are more likely to have definite RHD and the relative risk is highest if the index case has definite RHD. Future screening programs should consider implementation of sibling screening following detection of an RHD positive child. Larger screening studies of adults are needed, as data on prevalence of latent RHD outside of childhood are sparse. Future studies should prioritize implementation research to answer questions of how RHD screening can best be integrated into existing healthcare structures, ensuring practical and sustainable screening programs.

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Section: Discussionmentioning

confidence: 99%

Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case

et al. 2016

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“…For the South Asian analysis, genetic material was obtained with informed consent from cases and controls recruited to two distinct studies. Specifically, we expanded an existing collection in Northern India [12][13][14][15][16], and we used samples from our existing collection of Pacific Islanders [8], specifically the Fijians of Indian descent. Cases of RHD were defined on the basis of: a history of valve surgery for RHD, a definite RHD diagnosis by echocardiography, or borderline RHD diagnosis by echocardiography with prior acute rheumatic fever [17].…”

Section: Sample Collectionsmentioning

confidence: 99%

“…In India, adults with incident or prevalent RHD were recruited as cases from a single large referral hospital, the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh; recruitment was limited to patients with an echocardiographic diagnosis of RHD [17]. Controls were recruited based on normal echocardiograms and the absence of prior family history of rheumatic fever [12][13][14][15][16]. In total, DNA samples were obtained from 543 cases and 397 controls.…”

Section: Sample Collectionsmentioning

confidence: 99%

The Human Leukocyte Antigen Locus and Susceptibility to Rheumatic Heart Disease in South Asians and Europeans

Auckland

Mittal

et al. 2019

Preprint

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Background. Rheumatic heart disease (RHD) remains an important cause of morbidity and mortality globally. Several reports have linked the disease to the human leukocyte antigen (HLA) locus but with negligible consistency. Methods. We undertook a genome-wide association study (GWAS) of susceptibility to RHD in 1163 South Asians (672 cases; 491 controls) recruited in India and Fiji. We analysed directly obtained and imputed genotypes, and followed-up associated loci in 1459 Europeans (150 cases; 1309 controls) from the UK Biobank study. For fine-mapping, we used HLA imputation to define classical alleles and amino acid polymorphisms. Results. A single signal situated in the HLA class III region reached genome-wide significance in the South Asians, and replicated in the Europeans (rs201026476; combined odds ratio 1.81, 95% confidence intervals 1.51-2.18, P=3.48x10-10). While the signal fine-mapped to specific amino acid polymorphisms within HLA-DQB1 and HLA-B, with conditioning, the lead class III variant remained associated with susceptibility (P=3.34x10-4), suggesting an independent effect. Conclusions. A complex HLA signal, likely comprising at least two underlying causal variants, strongly associates with susceptibility to RHD in South Asians and Europeans. Crucially, the involvement of the class III region may partly explain the previous inconsistency, while offering important new insight into pathogenesis.

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“…Single-nucleotide polymorphisms in a number of genes were found in patients with RHD compared to controls, namely protein tyrosine phosphatase non-receptor 22 (PTPN22), 41 signal transducers and activators of transcription (STAT), 42 angiotensin converting enzyme (ACE I/D), 43 TNF-α, 44 , 45 transforming growth factor (TGF-β1), 46 , 47 and TLR5 48 (Table 2) . Studies in North Indians with RHD suggest that the (PTPN22) haplotype, which encodes an important negative regulator of T-cell activation, modulates the risk of developing RHD.…”

Section: The Role Of Genetic Studiesmentioning

confidence: 99%

“…Studies in North Indians with RHD suggest that the (PTPN22) haplotype, which encodes an important negative regulator of T-cell activation, modulates the risk of developing RHD. 41 In a Turkish population, however, it was demonstrated that the PTPN22 R620W polymorphism was not associated with RHD, 49 showing that genetic differences exist among populations from different regions of the world, therefore making it relevant to implement similar studies in Africa.…”

Section: The Role Of Genetic Studiesmentioning

confidence: 99%

Rheumatic heart disease in Africa: is there a role for genetic studies? : review article

Mocumbi¹

2015

CVJA

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Rheumatic heart disease (RHD) constitutes a leading cause of premature death and incapacity in Africa, where it is encountered in younger people, and shows a much faster and more malignant course than that seen in Europe or North America. While it is well established that RHD is a consequence of recurrent, untreated group A β-haemolytic streptococcal infections (GAS), the pathogenesis is incompletely understood, and the variation in natural history and phenotypes are not fully explained. In Africa patients are rarely diagnosed with acute rheumatic fever (ARF). They usually present in the late stages of RHD, with the severe and virulent forms occurring at early ages, therefore leading to high morbidity and mortality in young patients.

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Influence of protein tyrosine phosphatase gene (PTPN22) polymorphisms on rheumatic heart disease susceptibility in North Indian population

Cited by 7 publications

References 25 publications

Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case

Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case

The Human Leukocyte Antigen Locus and Susceptibility to Rheumatic Heart Disease in South Asians and Europeans

Rheumatic heart disease in Africa: is there a role for genetic studies? : review article

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