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Table 1.  

Association LOD Score Gene
1q22-24 3.45 FCGR 2A/3A
1q31 3.79  
1q41-42 3.3 SLEB1 locus
2q35-37 4.24 PDCD1, SLEB2 locus
4p16-15 3.84  
6p22-21 4.19 HLA-DR, DQ, C4, TNF
12q24 3.72  
16q12-13 3.85  

Susceptibility Loci for SLE

SLE = systemic lupus erythematosus; FCGR 2A/3A = Fc gamma receptor 2A/3A; HLA = human histocompatibility antigen; C = complement; PDCD = program cell death; TNF = tumor necrosis factor

Table 2.  

Chromosome Population Effect
6p21, MHC region United States; n, 266 pts LOD score > 3
6q27 United States; n, 266 pts LOD score > 3
19q13 United States; n, 266 pts LOD score > 3
12q23-24 United States; n, 266 pts Association
16p13 United States; n, 266 pts Association
7q21 United States; n, 266 pts Association
13q33-34 United States; n, 266 pts Association
Osteopontin polymorphisms United States; n, 821 No genetic association
Osteopontin wild-type 1284A allele United States; n, 821 Trend of increased risk for secondary progressive disease
2p, 3q, 5q, Xp United States; 98 families; France; 90 families Previously reported linkage not confirmed
1p34 United States; 98 families; France; 90 families LOD score > .9
3p14 United States; 98 families; France; 90 families LOD score > .9
19q13 United States; 98 families; France; 90 families LOD score > .9
17q11, NOS2A locus, D346D 2 African American data sets Association
17q22-24, PRKCA polymorphism United Kingdom; n, 184 Association
6p Canada; n, 552 affected sibling pairs LOD, 4.4
2q27 Canada; n, 552 affected sibling pairs LOD, 2.27
5p15 Canada; n, 552 affected sibling pairs LOD, 2.09
18p11 Canada; n, 552 affected sibling pairs LOD, 1.68
9q21 Canada; n, 552 affected sibling pairs LOD, 1.58
1p31 Canada; n, 552 affected sibling pairs LOD, 1.33
17q Canada; n, 552 affected sibling pairs LOD, 1.67
DRB1*15 Continental Italy; n, 609 Association; odds ratio, 3.64
DRB1*07 Continental Italy; n, 609 Negative association; odds ratio, .60
6p21.3 (the HLA region), 6q14.1 and 7q34 Portugal; n, 200 Association
6p21 Germany; n, 234 and Finland; n, 195 Association
7p15 France and United Kingdom; 104 families Association in HLA-DR15-negative patients
5p15 Turkey; n, 197 Association

Susceptibility Loci for Multiple Sclerosis

HLA = human histocompatibility antigen


Genes and Autoimmune Diseases -- A Complex Inheritance

  • Authors: Sara M Mariani, MD, PhD
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Target Audience and Goal Statement

This activity is intended for primary care physicians, rheumatologists, and other physicians who care for patients with autoimmune diseases.

The goal of this activity is to review current evidence describing the role of genetics in autoimmune diseases.

Upon completion of this activity, participants will be able to:

  1. Comment on the general relationship between genetics and autoimmune diseases.
  2. Identify mediators of rheumatoid arthritis.
  3. Describe the association of the PTPN22 allele with rheumatoid arthritis.
  4. Identify genetic and other factors involved in the development of systemic lupus erythematosus.
  5. Specify factors of inheritance of multiple sclerosis.


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Medscape encourages Authors to identify investigational products or off-label uses of products regulated by the U.S. Food and Drug Administration, at first mention and where appropriate in the content.


  • Sara M Mariani, MD, PhD

    Deputy Editor, Medscape General Medicine; Site Editor/Program Director, Medscape Molecular Medicine


    Disclosure: Sara M. Mariani, MD, PhD, has no significant financial interests or relationships to disclose.

CME Author(s)

  • Charles P Vega, MD

    Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine


    Disclosure: Charles Vega, MD, FAAFP, has disclosed that he has received grants for educational activities from Pfizer.

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Genes and Autoimmune Diseases -- A Complex Inheritance

Authors: Sara M Mariani, MD, PhDFaculty and Disclosures


The Genetics of Autoimmune Diseases

The fly sat upon the axle-tree of the chariot-wheel and said, "What a dust do I raise!"
Francis Bacon

About 3% to 5% of the US population is affected by an autoimmune disease, such as rheumatoid arthritis (RA), multiple sclerosis (MS), or systemic lupus erythematosus (SLE). Although it is still unclear what these diseases may have in common, they are generally grouped in the autoimmune category, as a dysregulation of the endogenous immune response (leading to damage of the patient's own tissues and organs) is thought to underlie their development and progression. RA and SLE predominantly affect the joints and the kidneys, whereas MS stems from demyelination in the central and peripheral nervous systems.

Far more women are affected than men, and heterogeneity in incidence is known to occur among different populations and different countries. MS, for example, manifests itself more frequently in young women of Northern rather than of Southern European descent. It is unclear whether such heterogeneity reflects genetic and/or environmental factors.

Cause and effect is still an elusive link in autoimmune diseases, and the therapies currently used reflect this lack of clear etiopathogenetic knowledge. All have a hereditary component, most probably polygenic in nature. Genetic regions and polymorphisms associated with each disease are being uncovered, and the most relevant were discussed at the 54th Annual Meeting of the American Society of Human Genetics, recently held in Toronto, Ontario, Canada.

Some gene associations have been confirmed, while others have been proven inconsistent or restricted to a specific population. More data will come in the near future, and they are expected to help in dissecting the genetic origin of autoimmune diseases and in unraveling their causes. In the meantime, we may want to remember that, sometimes, linkages and gene associations may just be flies sitting on a chariot wheel.