The association between HLA antigens and ageing is not clear. Ageing in wom
en was associated with B40 and DR5 in a recent study, but other studies yie
lded conflicting results. In none of the studies, however, did the young an
d elderly samples originate from the same homogeneous population. Homogenei
ty is dependent on geographic origin. The aim of this study was to investig
ate whether differences in geographic origin between age groups could expla
in the age-associated differences in the frequencies of B40 and DR5. The au
thors used the new design of a 'birth-place-restricted comparison' in which
the origin of all subjects was ascertained. The total study population com
prised 1010 young women aged 25-40 years and 660 elderly women aged 85 year
s and older. The 'birth-place-restricted comparison' included 66 young and
285 elderly women from one geographic area (Leiden, the Netherlands). Men w
ere not included because ageing in men was not associated with HLA antigens
in a recent study. In the total population, the frequency of B40 in young
women of different origin varied between 16 and 28%, and the frequency of D
R5 between 11 and 23%. Similar differences were observed in the elderly wom
en. In the 'birth-place-restricted comparison', the frequency of B40 was 15
% in the young women and 11% in the elderly women (difference 4%, 95% confi
dence interval, -5 to 13%). The frequency of DR5 was 20% in the young women
, and 28% in the elderly women (difference 8%, 95% confidence interval, -4
to 19%). Thus, marked differences in HLA antigen frequency were found betwe
en populations of various geographic origins. Definition and ascertainment
of the target population are therefore necessary in genetic studies of agei
ng. In such a 'birth-place-restricted comparison', the authors confirmed th
at ageing in women was negatively associated with HLA-B40 and positively as
sociated with HLA-DR5.