Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2‐macroglobulin and tau: A population‐based autopsy study

Figures & data

Table Ia. The study subjects stratified by age at death, gender, and grade of senile systemic amyloidosis.

	SSA grade (0–3)	Age at death (years)
		85–89.9	90–94.9	95–99.9	⩾100
Men	3	1	2	1	0
	2	0	0	1	0
	1	0	7	2	0
	0	10	11	7	0
Women	3	0	1	1	1
	2	1	3	2	0
	1	9	16	11	4
	0	44	87	31	3

Table Ib. Demographic and health‐related characteristics of individuals with and without senile systemic amyloidosis.

	Study population	SSA+	SSA−	P‐value
n	256	63	193
Men, %	16	22	15	0.151
Age at death, years ^a	92.5±3.8	93.8±4.3	92.0±3.5	0.002
Heart weight, g ^a	356.6±89.5	381.7±106.6	348.8±81.9	0.015
BMI category ^a	3.0±0.7	2.85±0.7	3.05±0.7	0.053
Myocardial infarction, %	40	50	37	0.076
Diabetes, %	22	21	23	0.720
Hypertension, %	29	31	28	0.687
Smoking in 1991, %	16	21	14	0.188

^a Mean (±SD). The P‐values are obtained when comparing the subjects with (+) and without (−) SSA, by using chi‐square or exact test for linear trend for categorical variables and logistic regression analysis for continuous variables.

SSA = senile systemic amyloidosis; BMI = body mass index (weight divided by height squared); BMI category = the BMI values as classified into five categories: 1⩾32; 2 = 28–31; 3 = 19–27; 4 = 15–18; 5⩽14.

Table II. The results of association analyses comparing the genotype distributions in subjects with and without senile systemic amyloidosis.

Gene/polymorphism	Chi‐square tests for linear trend	Df	P‐value
Angiotensin converting enzyme
Insertion‐deletion	0.122	1	0.727
Alpha2‐macroglobulin
Exon 24 (Ile1000Val)	4.116	1	0.042
Intron17/Exon 18 (5 bp del)	2.222 ^a	1	0.167
Apolipoprotein E
ϵ2/3/4	3.891 ^b	5	0.559
Promoter ‐219	0.010	1	0.921
Promoter ‐491	0.008 ^a	1	1.000
Intron IE1	0.270	1	0.604
Beta‐amyloid cleaving enzyme2
Intron 1a	0.498	1	0.480
Intron 1b	0.231	1	0631
Exon 6	1.392	1	0.238
Exon 8	0.217	1	0.641
Lipoprotein lipase
Ser447Ter	0.382 ^a	1	0.680
Asn291Ser	0.335 ^a	1	0.734
Low‐density lipoprotein receptor‐related protein
Exon 6	0.003 ^a	1	1.000
Prion protein gene
C129 M/V	1.657	1	0.198
Tau
H1/H2	6.515 ^a	1	0.016
RS3785883	0.266	1	0.606
RS2471738	0.040	1	0.841
RS7521	3.243	1	0.072

The values presented have been obtained by comparing the genotype distributions in subjects with and without senile systemic amyloidosis, by using chi‐square tests for linear trend.

^a Values are obtained by exact test for linear trend.

^b Values by Fisher's exact test.

Df = degrees of freedom.

Table III. Comparison of genotypes of the alpha2‐macroglobulin exon 24 and tau H1/H2 polymorphisms in subjects classified according to the severity (grade) of senile systemic amyloidosis.

	SSA grade
	0	1	2	3
Gene/genotype
α2M
A/A	60 (83%)	11 (15%)	0 (0%)	1 (1%)
A/G	81 (70%)	26 (22%)	5 (4%)	3 (3%)
G/G	25 (68%)	7 (19%)	2 (5%)	3 (8%)
				χ^2 = 6.518, 1 df, P = 0.012 ^a
Tau
H1/H1	136 (76%)	35 (20%)	3 (2%)	4 (2%)
H1/H2	15 (58%)	7 (27%)	1 (4%)	3 (12%)
H2/H2	1 (33%)	1 (33%)	1 (33%)	0 (0%)
				χ^2 = 8.842, 1 df, P = 0.003^b,c

SSA grades 2 and 3 were pooled in all statistical analyses.

^aP‐value from exact test for linear trend.

^bP‐value from Chi‐squared test for linear trend.

^c H1/H2 and H2/H2 groups were pooled in the statistical analysis.

SSA = senile systemic amyloidosis; df = degrees of freedom; α2M = alpha2‐macroglobulin.

Table IV. Results of a multivariate analysis assessing the effects of age, myocardial infarctions, and the genetic variants of alpha2‐macroglobulin and tau on senile systemic amyloidosis.

	Odds ratio	95% Confidence interval	P‐value
Age at death	1.101	1.000–1.211	0.050
Myocardial infarcts	2.727	1.378–5.399	0.004
Alpha2‐macroglobulin exon 24	1.673	1.025–2.731	0.040
Tau haplotype	2.889	1.202–6.944	0.018

Logistic regression analysis with stepwise selection method was used in this analysis.