”…Many of the genes responsible for the functioning of the immune system are located on the X chromosome. As females have two X chromosomes, whilst men only have one, they are more likely to inherit gene mutations that cause immune dysfunction. It is also recognised that hormonal activity is an important trigger. Lupus can often develop around puberty, after childbirth, during menopause and usually occurs in females between the ages of 15 to 55.”
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I’ve been thinking about the above statement now for sometime and I know there has been much discussion on the genetics of lupus and am wondering whether the above statement needs updating?
Any answers to these questions please?
1. Women have two X chromosomes in their cells. Surely if only one X chromosome has got the gene mutation that causes lupus then shouldn’t the healthier X chromosome take over or mask the other one so lupus is NOT expressed in that person. What if gene mutations causing lupus are found in both X chromosomes? Just pondering. Will you definitely get lupus?🥹
2. Men have only ONE X chromosome which presumably is inherited from their mothers. Apparently no genetic mutations for lupus are found on the Y chromosome so can we say that lupus in men has some sort of mother-son genetic inheritance? IDK that environmental factors do play a part in bringing about lupus but surely gene mutations play a greater part?
3. Has this lupus gene mutation now been identified?
Perhaps some clever posters on here with greater knowledge on the genetics of lupus can explain?🧐
Thanks.
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Betty909090
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Very good question - be glad to hear and one with the smarts give their insight. I did wonder about the genetics as no one in our families (on either side/ male or female) have had lupus that I know of - yet my daughter has been diagnosed.
And in hindsight (had I knew much more about Lupus other than the name) I may have realised she grew up with possible symptoms showing, which to me were all explained away by other things but looking back can see ALL the signs were just simmering away.
So wondering how it showed up in her - are genetics involved somewhere?
I think you’re possibly pointing at “latent”/grumbling lupus in your daughter’s case which Dr Kaul (international expert) has often referred to in one of his YouTube channels?
I’m wondering if one is carrying the genetic mutation whether an environmental trigger makes it full “blown” overt lupus?
However my post is all about the genetic basis to lupus.
Hi Betty. I’m politely curious as to your wondering regarding the genetic causes or causes of lupus. Google searches reveal the progress of this;albeit slowly. Finding causes =finding cures? Personally I’m not seeking genetic causes(although autoimmune issues are prevalent in family history). I am more concerned with day to day treatment of myself to live my best life with hope that the science based community will solve these puzzles/ and making evidence based information about lupus known to my grown children. 🌼MM
If you read my original post carefully I’m wondering about the LUPUS website info on this genetic mutation on the X chromosome.
My questions noted above as 1, 2 and 3 are still relevant but no one has as yet posted convincing answers.
BTW your “finding causes=finding cures” IMO does not equate?
Surely someone somewhere has found/identified this genetic mutation on the defective X chromosome and has elucidated how it functions/brings about lupus in us sufferers?
I feel like you that the genetics of Lupus could be updated in that the info you’ve copied and pasted from the LUPUS UK website is probably over a decade old?
Just a footnote: a recent review article in Nature (Ghodke-Puranik et al 2024) states that "Genome-wide association studies have identified almost 200 SLE-associated risk loci, yet unravelling the functional effect of these loci remains a challenge". Elsewhere, I've read that the methylation state of certain loci is key to whether or not auto-immune reactions are triggered. (i.e. the mere presence of the relevant allele may not be enough).
So it seems unlikely its a question of X chromosome inheritance alone. Much more likely is that a complex interplay between multiple genes and factors in the environment will determine whether auto-immune reactions are triggered - even if the hormonal environment (including sex-linked hormones) might play a significant role. x
You’ve said much more than what I found published on this website!
Sadly even though one has the genetic mutations which predispose us to lupus it’s the numerous “environmental “ triggers that tip our bodies into full blown lupus of whatever manifestation? Stress or our reactions to various stressors can tip some into a diagnosis of lupus?
Perhaps identical twin studies in relation to lupus might cast some light on what these environmental triggers are!🧐
Hi Betty. Here you have mentioned “stressors” that may cause gene mutations or push us over the edge: environmental. I know many here on the forum can relate to viral infections as”stressors “ that weakened immunity to other diseases. My own daughter had mononucleosis at 17 and 21. Now in her 30’s her health has never been restored. And I think back to my own childhood in the 1960s. Some viral ailments had no name. But clearly as a child I had “something.”
Also, environmental stressors as you mention is such a broad term I feel the need to liquidate it a bit: child abuse. Severe child abuse has been determined to cause lupus. I don’t have the research here to print for you; but I suspect with your broad knowledge you know this already and can read with google search. I’m one of those kids. When I read “environmental “ stressors, which is scientifically correct, I think many people with lupus need to see, read, hear that their disease; their dysfunction, was beyond their control. The mind /body connection is indeed a “gene splicer.” Look what psychology has discovered about multiple personalities!
Last, lupus is not as sexy as multiple personalities but it is finally becoming studied with diligence (I think and hope)..And you are right I missed what you said regarding the website needing updating. Perhaps the ambiguity of Lupus itself is responsible for its own lack of definition. Best, MM
Glandular fever (mononucleosis) is caused by the Epstein-Barr virus which sadly persists in one’s body despite recovery!😨
Like you, I too have a daughter who caught glandular fever at 19. She’s now in her 40s and one wonders whether what stressors/experiences she may encounter in life to push her body into developing a full blown AI inflammatory disease like lupus? 🤔
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It would be very interesting to hear from men out there and whether they were sent for a physiological assessment at any stage? 
The MTHFR gene: Have you run into this?
Anyone out there with Psoriatic Arthritis and Lupus? How was your PsA diagnosed? How is it diagnosed as different from OA? 
Just out of Curiosity, what age did you feel you started with Lupus signs and symptoms? Age of diagnosis?
