An increase in heterozygosity, mostly at the HLA-B locus, in older age groups been reported, but other studies have not confirmed this observation. 11,1s~19

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In the authoritative book HLA and Disease Associations,L’i n the chapter diseases” a paragraph is devoted to the subject of “age” in of association with HLA antigens. A meta-analysis on HLA-B40 with the combined data of eight independent studies. The result was significant increase in the frequency of B40. Thk increase in the was primarily a consequence of the data of Macurova” and remarks were made concerning some of the studies, and we quote: “The frequency of B40 in the old group may be an artifact of sample size, HLA serology, and typing techniques”.

These discrepancies prompted us to reinvestigate the association of HLA antigens with survival. We performed a study of the HLA phenotypes of all available inhabitants, that is, 964 persons, aged 85 years and over of the commu- nity of Leiden, the Netherlands. The frequencies of HLA antigens were com- pared with a control group, consisting of 2444 blood donors, 20-35 years of age, with an identical ethnic (Dutch Caucasoid) and geographic background. Also, control groups of different age brackets were used from the same region.

SUBJECTS AND METHODS

On the entry date of December lst, 1986, the total cohort of inhabitants of Leiden, aged 85 years and over comprised 1259 subjects. From January 1987 until March 1989, 977 individuals of this age group were visited at their place of resi- dence. After appropriate informed consent was obtained, a medical history was taken and blood was drawn by venipuncture for HLA typing. A total of 222 persons had died before they could be visited and 60 persons did not cooperate. Blood samples for HLA typing were obtained from 964 persons.

A large database was available with HLA typings of blood donors of different ages from the same geographical district. We chose the age group of 20-35 be- cause the mortality rate is lowest at these ages. These subjects have survived the diseases of childhood and have yet to encounter diseases of middle age: malignan- cies, cardiovascular disorders and autoimmune diseases. The database of HLA typings of the blood bank was also used to generate control groups of diffcrent age-brackets from identical ethnic and geographic background.

To obtain an ethnically homogeneous sample, nine elderly subjects of non- Caucasoid parentage (data obtained during personal visit or from family) were excluded. Four of these excluded subjects were of Indonesian (oriental) parent-

LAGAAY et al.: LONGEVITY & HEREDITY

four of Surinamese (negroid, or mixed oriental/negroid) and one of Chinese

These selection and exclusion procedures resulted in 964 HLA typings of subjects of 85 years and older, and 2444 of 20-35 years of age. The number of HLA typings of the different age groups are: newborns n = 476; 20-29 years n = 1311; 30-39 years n = 2143; 40-49 years n = 1477; 50-59 years n = 354; 60-84 =

Methods

Typing for the HLA-A, B and C (class I) antigens was performed with the standard lymphocytotoxicity test, and typing for HLA-DR and DQ (class 11) antigens with a two-color fluorescence test using a set of highly selected alloanti- sera to class I1 antigens.

(pat. with AG) x (contr. without AG) RR = (pat. without AG) x (contr. with AG) = patient; contr. = control; AG = HLA antigen

pat. = patient; contr. = control; AG = HLA antigen

test for 2 x 2 contingency tables. The ages of the subjects for the analysis were taken as their ages at the time of collection of the blood sample for HLA typing.

The results of HLA typing of 48 antigens are listed in TABLEI . The distribu- tion of HLA antigens in the study population was in good general agreement with that in the control group with two exceptions: the frequency of HLA-B40 was lower and that of HLA-DR5 was higher in the age group of 85 years and over. After correction for the number of antigens tested, these differences were statisti- cally significant in females only (TABLE2S a nd 3). The changes appeared gradually with age, as shown in FIGURE1. The percentages of homozygotes were not different between the young and old

The percentages of homozygotes were not different between the young and old age groups (data not shown).

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