Risk of type 1 diabetes in childhood and maternal age at delivery, interaction with ACP1 and sex.
BACKGROUND
We have investigated the possible role of ACP1 (also known as cLMWPTP: cytosolic low molecular weight phosphotyrosine phosphatase), a highly polymorphic enzyme involved in signal transduction of T-cell receptor, insulin receptor and other growth factors in the relationship between maternal age at delivery and risk of type 1 diabetes in the offspring.


METHODS
One hundred and eighty-nine consecutive children with type 1 diabetes (TIDM) diagnosed at the Department of Pediatrics of the University of Sassari (Sardinia) were studied. A control sample of 5460 consecutive newborns from the same population was also studied.


RESULTS
Maternal age at birth of children with type 1 diabetes has shifted towards high values. There is also an effect of birth order on the susceptibility to type 1 diabetes, which is independent of that due to maternal age. The proportion of low activity ACPl genotypes is much higher among children born from older mothers than among diabetic children born from relatively young mothers. There is a significant effect of sex, maternal age, sex-ACPl two-way interaction and sex-ACP1-maternal age three-way interaction on the age at diagnosis of diabetes.


CONCLUSIONS
The present data confirm the strong association between maternal age at delivery and risk of type 1 diabetes in the child. In addition, our analysis suggests a complex interaction among maternal age, sex of infant and ACP1 concerning age at diagnosis of diabetes. Thus, risk and clinical course of type 1 diabetes seem to be dependent on both maternal environment during intrauterine development and foetal genetic factors.
Bottini
N
N
Burhnam Institute, La Jolla, California, USA.
Meloni
G F
GF
Lucarelli
P
P
Amante
A
A
Saccucci
P
P
Gloria-Bottini
F
F
Bottini
E
E
D000328:Adult; D002648:Child; D036861:Delivery, Obstetric; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors
D007527:Isoenzymes; D011518:Proto-Oncogene Proteins; C490429:ACP1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases