^^^^^^GREETINGS FROM^^^^^^^^^^
Ivan Suzman 47/10 [log in to unmask]
Portland, Maine land of lighthouses 50 deg. F nippy, lilac-scented
air
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Dear Listfriends,
This is my 10th and FINAL (hooray!) post on the intriguingly frequent
occurrence of diabetes in the families of PWP's.
What I hope to do here is share a few new ideas about the
INHERITANCE of PD and diabetes, that emerge from the "DIABETES SURVEY"
responses that 102 of you sent to me.
I am very grateful to the few of you who have taken the time to
write comments on parts 1 through 9 of the Survey, posted between
Friday, May 23 and Tuesday, June 3, 1997, AND I HOPE THIS DISCUSSION
CONTINUES.
I wish I could follow up your suggestions for further work, but I
need now to save my energy for moving back home during the weekend of
June 28-29, after an exhausting 11-month ordeal since my home burned on
Wednesday evening, August 7, 1996.
The sub-floors are now going in, and the carpeting, tilework and
linoleum are scheduled to start on Wednesday.
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Back to the Diabetes Survey. HERE ARE THE MAIN POINTS:
:
Diabetes occurs in 62% of the families of the 102 PWP's on the
Parkinson's List who responded.. This sample of 102 of us is not a random
selection of all PWP's on Earth. However, 62% is high enough to support
the idea that a genetic PD-diabetes linkage is probable.
One possible explanation is that a mutated or rare gene(s) that
might cause a PWP's dopamine deficiency (PD), could also influence that
PWP's adrenalin supply. Dopamine converts to noradrenalin, which in turn
converts to adrenalin. If the dopamine supply is abnormal, could this
upset the adrenalin supply?
Meanwhile, insulin, needed to avoid diabetes, is inhibited by
adrenalin. Blood sugar abnormalities like diabetes might be expected in
higher than normal frequency in the PWP's when their adrenalin supply is
genetically disrupted.
Part 3 showed that 9 of us have already developed diabetes. By
the end of the lifetimes of the 102 of us, who knows how many more will
become diabetic? Also, one person had diabetes during pregnancy, and one
more is hypoglycemic.
We PWP computer-users are a YOUNG sample of Parkinsonians. Part 9
showed that our average age at onset is in the early fifties. The PWP's
without a diabetic relative are slightly older at PD onset, at 53.4 years
age. Those of us with one or more diabetic relatives averaged 51.6 years
for age of PD onset.
So, we can expect that the 11 of us ( Phil Lammers, Jeannie
Ecklund's mom, Ruth Evan's brother, Bill Butch, Ruth Henry, Don Mckinley,
Phil Tompkins, Mary Helen Davila, Ellen Figura, Dale Severance, and Milo
Anderson) who are PWP 's and have a blood sugar abnormality, will be
joined by many others, unfortunately, as our lives go on.
Diabetic brothers and sisters, ranging from Barbara Patterson's
four (a sister, and three brothers), to many of us with one diabetic
sibling, are found in 13 of us. Part 5 shows that 10 women on our List,
or 40% of the 25 women with diabetic relatives, have an affected sibling,
but only 3 males of 37 (8%) have a diabetic sibling. Clearly, in our
sample, the FEMALE PWP's are far more likely to have a diabetic brother
or sister.
This preponderance of female PWP's with diabetic siblings over
male PWP's with diabetic siblings, 40% versus 8 %, is rather striking.
One wonders, why is this so? Could it be that the PD gene, or
at least one of the genes, is on the chromosomes of both parents of the
female PWP with diabetic relatives? I really don't know why there is
such an obvious male PWP-female PWP difference.
Matrilineal inheritance, which Margie Swindler commented on,
is obviously dominant in our PWP sample. Does this suggest that the X
chromosome is involved in the inheritance of the dopamine undersupply
characteristic of PD, and the perhaps linked adrenalin disruption of the
diabetic relatives of the PWP's?
Part 2 showed that 66% of the female PWP's and 59% of the
male PWP's have a diabetic relative. Part 4 showed that there were 22
males and 13 females with MATERNAL diabetic relatives, but only 11 males
and 9 females with paternal diabetic relatives. That is a total ratio of
35 PWP's with maternal relatives, and just 20 PWP's with paternal
diabetic relatives.
Part 6 continues the theme of FEMALE/MATRILINEAL dominance.
19 of our mothers, but only 8 of our fathers are reported to have been
diabetic.
More than half of the female PWP's (13 of 25) with a diabetic
relative have a diabetic parent. Only 14 out of 37 male PWP's are sons
of a parent. who developed diabetes. This is a 52% to 38% female to male
ratio.
Part 7 reinforces MATERNAL (matrilineal) inheritance of the
PD-diabetes linkage. There are 21 diabetic aunts. 13 are our mother's
sisters. Only 8 are our father's sisters.
With uncles, similarly, of 12, 8 are maternal, and only 4
are paternal. All totalled, there are 13 + 8 = 21maternal aunts or
uncles, but only 8 + 4 = 12 paternal aunts and uncles.
Thus, the maternal to paternal ratio is 21 to 12.
Moreover, of the 12 female Listmembers with a diabetic
aunt or uncle, 10, or 83%, have an affected MATERNAL aunt or uncle.
This is almost certainly a non-random pattern, even if
our sample of 102 PWP's is not a random sample. Findings like these, I
think, should alert us that maternal-relative dominance is quite probably
involved in the family patterns of PWP's with diabetic relatives.
Part 8 tells the same story. There are 17 grandmothers
but only 5 grandfathers reported to have been diabetic. This means that
a whopping 82% of the diabetic grandparents are Listmembers'
grandMOTHERS.
Another hint at the genetic mysteries involved is that
67.2% (29 of 43) of the PWP's with onset by age 50 have diabetic
relatives, slightly greater than the 56.8%, 25 of 44, of the older than
50 at onset group of PWP's.
I am a good example of this tendency. I had PD onset at
age 37; my older brother was already diabetic in 1961, at age 16.
I have always felt that his diabetes (could it be an
insulin imbalance due to an adrenalin disruption?) and my PD (due to a
dopamine loss), are part and parcel of the effects of the same gene, or
set of genes, that he and I both inherited.
What I mean is that perhaps in ALL 63 of 102 PWP's with
one or more diabetic relative, it is an inherited, often matrilineal,
gene or genes, that is involved in both our own Parkinson's and our
family member's blood-sugar disturbance.
Last year, we talked about th English study that showed
that 50 to 80% of British PWP;'s have ABNORMAL blood sugar tolerance test
results.
There is a lot of food for thought here. I will stop
now. Thank you again for listening. Hopefully, my survey will be taken
further by some tireless soul, and we will get closer to unraveling the
mysterious genetic story of both Parkinson's and diabetes....
Ivan Suzman
Portland, Maine
