Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus

Adrianto, Indra,Wen, Feng,Templeton, Amanda,Wiley, Graham,King, Jarrod B,Lessard, Christopher J,Bates, Jared S,Hu, Yanqing,Kelly, Jennifer A,Kaufman, Kenneth M,Guthridge, Joel M,Alarc처n-Riquelme, Mart Nature Publishing Group, a division of Macmillan P 2011 Nature genetics Vol.43 No.3

Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 ? 10<SUP>??8</SUP>, odds ratio = 1.70) and Korean (P = 8.33 ? 10<SUP>??10</SUP>, odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-觀B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.

Association of two independent functional risk haplotypes in <i>TNIP1</i> with systemic lupus erythematosus

Adrianto, Indra,Wang, Shaofeng,Wiley, Graham B.,Lessard, Christopher J.,Kelly, Jennifer A.,Adler, Adam J.,Glenn, Stuart B.,Williams, Adrienne H.,Ziegler, Julie T.,Comeau, Mary E.,Marion, Miranda C.,Wa Wiley Subscription Services, Inc., A Wiley Company 2012 Vol.64 No.11

<P><B>Abstract</B></P><P><B>Objective</B></P><P>Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome‐wide association studies have identified >30 SLE susceptibility genes. One of these genes, <I>TNIP1</I>, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting NF‐κB signaling. The present study was undertaken to investigate the genetic factors that influence association with SLE in genes that regulate the NF‐κB pathway.</P><P><B>Methods</B></P><P>We analyzed a dense set of genetic markers spanning <I>TNIP1</I> and <I>TAX1BP1</I>, as well as the <I>TNIP1</I> homolog <I>TNIP2</I>, in case–control populations of diverse ethnic origins. <I>TNIP1</I>, <I>TNIP2</I>, and <I>TAX1BP1</I> were fine‐mapped in a total of 8,372 SLE cases and 7,492 healthy controls from European‐ancestry, African American, Hispanic, East Asian, and African American Gullah populations. Levels of <I>TNIP1</I> messenger RNA (mRNA) and ABIN1 protein in Epstein‐Barr virus–transformed human B cell lines were analyzed by quantitative reverse transcription–polymerase chain reaction and Western blotting, respectively.</P><P><B>Results</B></P><P>We found significant associations between SLE and genetic variants within <I>TNIP1</I>, but not in <I>TNIP2</I> or <I>TAX1BP1</I>. After resequencing and imputation, we identified 2 independent risk haplotypes within <I>TNIP1</I> in individuals of European ancestry that were also present in African American and Hispanic populations. Levels of <I>TNIP1</I> mRNA and ABIN1 protein were reduced among subjects with these haplotypes, suggesting that they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression.</P><P><B>Conclusion</B></P><P>Our results confirm the association signals between SLE and <I>TNIP1</I> variants in multiple populations and provide new insight into the mechanism by which <I>TNIP1</I> variants may contribute to SLE pathogenesis.</P>

부분 영역안의 표준편차를 사용한 두 단계 문자 이진화 방법

Adrianto Tedjokusumo,정헌,이상웅 한국차세대컴퓨팅학회 2013 한국차세대컴퓨팅학회 논문지 Vol.9 No.4

일반적으로 인쇄된 문자를 추출하는 문제에 있어서 비균일한 조명과 선명도는 이진화 결과에 많은 영향을 주게 된다. 특히 비강체 표면에서의 문자 추출은 비강체의 전형적인 특징으로 인해 이진화 결과가 좋지 않다. 본 논문에서는 비강체 표면에서도 강인한 문자 추출 방법을 제안한다. 제안된 방법은 문자 추출과 추출된 문자의 검증의 2단계로 구성된다. 첫 번째 단계에서는, 배경과 문자를 구별하기 위해서 가로, 세로 양방향의 표준 편차를 고려한 국부적 임계값을 적용한다. 또한 이러한 방법은 국부적 영역안에서의 최대, 최소 밝기값과 조명 분포을 고려하여 각 화소별 최적의 이진화 임계값을 선택하며, 계산 속도를 위하여 최적화하는 과정을 거치게 된다. 더불어 가로, 세로 양방향에 대한 표준편차 분석법은 문자영역과 문자의 위치를 검색하는 데 사용되며 적응적 이진화 결과를 개선시킨다. 두 번째 단계에서는 미리 정의된 문자의 너비, 높이, 분포 등의 규칙에 의해서 추출된 문자를 검증하게 된다. 본 논문에서 제안된 이진화 방법은 문자 인식 엔진에 적용되어 실험한 결과 다양한 환경에서도 좋은 결과를 보여주었다.

Depression in pregnant and postpartum women during COVID-19 pandemic: systematic review and meta-analysis

Nicholas Adrianto,Josephine Caesarlia,Fegita Beatrix Pajala 대한산부인과학회 2022 Obstetrics & Gynecology Science Vol.65 No.4

Coronavirus disease 2019 (COVID-19) emerged as a global pandemic in March 2020 and caused a big crisis, especiallythe health crisis. Pregnant and postpartum women experienced significant physical, social, and mental changes thatput them at higher risk for several conditions during the pandemic. This study aimed to report the prevalence ofdepression in pregnant and postpartum women during the COVID-19 pandemic. Eligible studies were identified usingseveral databases. Prevalence analysis was conducted using MedCalc ver. 19.5.1. This systematic review and metaanalysiswas registered in PROSPERO on July 12, 2021 with registration number CRD42021266976. We included 54studies with 95.326 participants. The overall prevalence of depression was 32.60% among pregnant and postpartumwomen during the COVID-19 pandemic. The rate was higher among pregnant women (31.49%) compared topostpartum women (27.64%). The prevalence of depression among pregnant and postpartum women increasedduring the COVID-19 pandemic. 영어

Identification of a Systemic Lupus Erythematosus Susceptibility Locus at 11p13 between <i>PDHX</i> and <i>CD44</i> in a Multiethnic Study

Lessard, Christopher J.,Adrianto, Indra,Kelly, Jennifer A.,Kaufman, Kenneth M.,Grundahl, Kiely M.,Adler, Adam,Williams, Adrienne H.,Gallant, Caroline J.,Anaya, Juan-Manuel,Bae, Sang-Cheol,Boackle, Sus Elsevier 2011 American journal of human genetics Vol.88 No.1

<P>Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10<SUP>−8</SUP>) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between <I>PDHX</I> and <I>CD44</I> showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10<SUP>−8</SUP>, OR = 0.83) and rs387619 (p = 7.7 × 10<SUP>−7</SUP>, OR = 0.83) in the European samples with p<SUB>meta</SUB> = 1.82 × 10<SUP>−9</SUP> for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10<SUP>−3</SUP>, OR = 0.81 and p = 4.3 × 10<SUP>−4</SUP>, OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p<SUB>meta</SUB> = 2.36 × 10<SUP>−13</SUP>. This locus contains multiple regulatory sites that could potentially affect expression and functions of <I>CD44</I>, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.</P>

Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Study

Marta E. Alarcon-Riquelme for the BIOLUPUS and GENLES Networks,Lessard, Christopher J.,Adrianto, I.,Ice, John A.,Wiley, Graham B.,Kelly, Jennifer A.,Glenn, Stuart B.,Adler, Adam J.,Li, H.,Rasmussen, A University of Chicago Press [etc.] 2012 American journal of human genetics Vol.90 No.4

Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; p<SUB>meta-Euro</SUB> = 2.08 x 10<SUP>-10</SUP>), transmembrane protein 39A (TMEM39A; rs1132200; p<SUB>meta-all</SUB> = 8.62 x 10<SUP>-9</SUP>), and 17q21 (rs1453560; p<SUB>meta-all</SUB> = 3.48 x 10<SUP>-10</SUP>) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 x 10<SUP>-8</SUP> < p<SUB>meta-Euro</SUB> < 9.99 x 10<SUP>-5</SUP>) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation.