Lupus Family History & Genetics -also could be any AI disease

[Guest guest]

This reminds me of RP too since they both are autoimmune diseases.

Systemic Lupus Erythematosus

Family History & Genetics - Complicated But Interesting

Lupus is a disease in which the immune system attacks normal tissues in the body. When the attack is directed at tissues in the joints, arthritis occurs. When the

attack is directed at the skin, a rash occurs. Each time we have a flare, tissues cells in the kidney, heart, brain, and elsewhere, can also be damaged.

Types of Lupus:

01. Systemic Lupus Erythematosus -- "systemic" means the disease is all over the body, "erythematosus" means "redness," describing the skin's appearance. And "lupus" comes from the Latin word for "wolf."

02. Cutaneous or Discoid Lupus -- Lupus that predominantly involves the skin.

03. Drug-induced Lupus -- Lupus that "can" appear after taking heart medicines procainamide and hydralazine. This type of Lupus usually goes away when the offending medication is stopped, although it sometimes takes years to resolve completely.

04. Latent Lupus -- an illness that is not quite Lupus, but does have many of the symptoms, and can later evolve into Lupus. Other names used are Mixed Connective Tissue Disorder (MCTD), Overlap Syndromes, Undifferentiated Connective Tissue Disease (UCTD), & Incomplete Lupus.

05. Neonatal Lupus -- seen in babies born to mothers who have lupus. Similar to Latent Lupus.

The pattern of immune attacks (flares) varies from person to person, and also in the same individual, over time. Lupus flares usually mimic each other, developing a pattern With each flare, but then the disease slowly progresses to getting worse, thus slowly changing this pattern to include other symptoms. The most common symptoms of Lupus are fever, rash, and arthritis.

The name Latin word "lupus," was used as far back as the 1700s to describe a variety of skin conditions, but the origin of the word was thought to describe a characteristic rash across the face which reminded some of the face of a wolf. Systemic Lupus Erythematosus was not classified as a separate disease until 1872.

In the 1950s, it was discovered that Lupus can run in families. Ever had a relative who complained of rheumatism?

Genetic information is coded in chromosomes which are located in humans, in a tiny part of the center (nucleus) of each cell. Humans have 46 chromosomes, each chromosome is made up of thousands of genes. Each chromosome is divided into a long and short arm. Most of the important genes in Systemic Lupus Erythematosus are located on the short arm of chromosome #6.

On the short arm of chromosome #6, is the HLA (human leukocyte antigen) region, which is located next to the area for "complement genes." The HLA is used to match donors genetically to recipients for organ transplants. This HLA is divided into smaller regions, called HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ.

In Lupus patients there is an increased frequency of the HLA genes called Al, B8, Dr2, or Dr-3 and DQ1. For unknown reasons, the HLA markers are found in white Lupus Patients, but not found in the Black or Japanese Lupus patients.

HLA class I genes -- have little to do with Lupus.

HLA class II genes -- many genes in this group are linked to Lupus. The combination of the DR3 and DQ2 variants, or the DR2 and DQ6 variants, raise the risk of Lupus by a factor of 2 or 3.

HLA class III genes -- Many genes in this group are linked to

Lupus. The C4A and C2 genes (complement genes), contain certain variants of the TNF genes raise the risk of Lupus in some ethnic groups.

For someone to inherit the susceptibility to develop Lupus, it is estimated they need the combination of 4 to 6 or more genes. It is nearly impossible to inherit all the genes necessary to develop Lupus, from a single parent, since an

individual's genes come from both parents. If only some of the Lupus genes are inherited, a person may not have Lupus but may have a positive immunologic test, such as the antinuclear antibody ANA. A positive ANA occurs in, up to, 1/3 of healthy family members of Lupus patients.

One part of the short arm of chromosome 1 was positive forLupus in 3 studies.

Regions on chromosomes 2, 6, 14, 16, and 20 also came up positive for Lupus, in at least two of the whole-genome studies.

The C1q genes on chromosome 1 sometimes code for a variant of the C1q complement protein that is less efficient than usual. When this happens, Lupus can result, especially in children. The C1q protein has both an "attack" function and a "clean-up" function in the immune system. Scientists believe that Lupus can be triggered if the remnants of an immune system attack are not cleaned up efficiently.

The C1q is the name for a complex of 3 different types of proteins, called A, B, and C. Each of these 3 proteins is made from its own gene on chromosome 1. Six copies of A, B, and C group together, meaning that C1q is actually a complex of 18 individual proteins! Scientists are not sure whether the A, B, or C gene causes the problem that leads to Lupus.

Deficiencies of other complement proteins, such as proteins coded by the C4A and C2 genes on chromosome 6, and the C1r and C1s genes on chromosome 12, also lead to Lupus development.

The MBL2 gene on chromosome 10 is the blueprint for a protein called mannose binding protein that is similar in shape to C1q. In Spanish and African-American populations, certain variants of the MBL2 gene are more common in persons with Lupus. Combinations of the MBL2 and the C4 gene are more strongly associated with Lupus than either gene alone.

The FCGR2A gene influences how the body cleans up the results of an immune attack (flare). Certain variants of this gene raise the risk of kidney disease in African-Americans with Lupus.

At least 2 genes have been found, which can contribute to the susceptibility to Drug-induced Systemic Lupus Erythematosus, when certain heart medications are taken.

The N-acetyl-transferase 2 gene on chromosome 8 influences how the body processes toxins. It plays a role in several human diseases. There are 2 major variants of the gene: "fast" and "slow." People with the "slow" variant are more likely to develop drug-induced Lupus.

The HLA class II genes on chromosome 6, are also involved. People with the DR4 variant are also more likely to develop drug-induced Lupus.

So, what is YOUR chances of developing Lupus?

01. The brother or sister of a Lupus patient is 25% more likely to develop Lupus than someone in the general population.

02. Lupus occurring in "more than one" family member, is 10% of the Lupus population.

03. If you have Lupus, there's a 5% chance that one of your siblings will develop Lupus also.

04. If one, of a pair of identical twins, (twins with exactly the same genes) has Lupus, the other identical twin has 2/3 chance or 57% to 69% chance of developing Lupus also.

06. If a fraternal or non-identical twin, (a twin with genes just like any other brother or sister sibling), has Lupus, the other fraternal or non-identical twin, has only 5% chance of developing Lupus also. (see #03)

07. Less than 5% of Lupus patients owe their genetic susceptibility to a single gene. Multiple genes are

usually involved.

08. "If" just one gene you could inherit, always caused Lupus, at least 1 out of 4 siblings should get Lupus, considering the classic laws of genetics.

09. 90% of all Lupus cases are in women. (Female hormones may help create the environment that allows a lupus gene to penetrate)

10. 10% of all Lupus cases are in men.

11. Certain men who have higher-than-normal levels of female sex hormones (due to a medical condition called Klinefelter Syndrome), develop Lupus at a rate between that of women and other men. (approximately 1 in 500 males with Klinefelter syndrome - also known as XXY males have an extra X chromosome)

http://www.hosppract.com/issues/1999/0915/cesmyth.htm

12. 10% of Lupus patients have an immediate family member with Lupus, 90% do not.

13. Lupus affects one out of every 1,000 white persons, and one out of every 250 black women from 18 to 65 years of age.

As in most human disease, Lupus has both strong "Genetic Components," and "Environmental Components" as well. It appears that some people are genetically predisposed to develop Lupus, but then must be exposed to the proper environmental triggers in order to have the disease.

Environmental triggers can be factors such as infections, such as the Epstein-Barr Virus, Ultraviolet radiation, diet, chemical agents and toxins. Research evidence is still weak and inconsistent in this area Lupus causes.

Conclusion - some family members will inherit genes that predispose to Lupus, and others will not. Some family members will be exposed to environmental agents that trigger disease, and others will not. Further discoveries about Lupus genes will lead to more individualized medicine. Prevention, diagnosis, treatment, and prognosis will be personalized, based largely on the strengths and weaknesses found in a person's genes.

References:

Genetics and Lupus by Dr. Raphael J. DeHoratius, MD

http://www.mtio.com/lupus/lal_4.htm

Genetics of Lupus - DNA Sciences Article

http://my.webmd.com/condition_center_content/lup/article/1823.50137

Genetic Basis of Lupus

http://www.elef.rheumanet.org/newsletter/5/nl5-22.htm