Disorder-specific effects of polymorphisms at opposing ends of the Insulin Degrading Enzymegene

BMC Medical Genetics

Table 2 Association results of insulin degrading enzyme haplotypes

haplotype				AD		Aβ₄₂plasma level [pg/ml]		T2DM
5' IDE2	IDE9	'3 IDE7	focus	OR (95% CI)	p-value	Slope (95% CI)	p-value	OR (95% CI)	p-value
T	A	A	baseline	2.01 (0.46 -9.47)	0.34	-5.8 (-16.1 - 4.5)	0.27	1.01 (0.63 -1.61)	0.98
T	A	A	1^st follow-up	1.96 (0.98 - 3.9)	0.06	-5.33 (-19.5- 8.86)	0.46	0.83 (0.5 - 1.38)	0.46
T	A	A	2^nd follow-up	1.51 (0.85 -2.68)	0.16	-7.37 (-24.7 -9.95)	0.41	0.92 (0.54 -1.59)	0.78
T	A × examination	A	longitudinal	0.94 (0.63 -1.41)	0.77	-0.05 (-0.18- 0.07)	0.4	0.95 (0.84 -1.07)	0.41
T	G	G	baseline	2.23 (0.82 -6.1)	0.12	-6.98 (-20.4- 6.47)	0.31	3.25 (1.31 -8.04)	0.01
T	G	G	1^st follow-up	1.03 (0.61 -1.74)	0.92	-6.78 (-25.1-11.6)	0.47	2.22 (0.81- 6.05)	0.12
T	G	G	2^nd follow-up	0.93 (0.56 -1.53)	0.78	-12.06 (-35.3-1.17)	0.31	3.28 (1.2 - 8.99)	0.02
T	G × examination	G	longitudinal	0.82 (0.59 -1.14)	0.25	-0.01 (-0.23- 0.21)	0.92	0.99 (0.79 -1.24)	0.93
T	A	G	baseline	0.91 (0.25 -3.26)	0.89	-0.62 (-17.9-16.7)	0.94	6.0 (1.29 -27.7)	0.02
T	A	G	1^st follow-up	1.22 (0.66 -2.26)	0.52	-0.75 (-25.13-23.6)	0.95	13.0 (1.47-129.33)	0.02
T	A	G	2^nd follow-up	1.02 (0.57-1.83)	0.94	-13.76 (-43-15.48)	0.36	8.66 (1.54 -48.77)	0.01
T	A × examination	G	longitudinal	0,99 (0.69- 1.43)	0.97	0.24 (-0.45- 0.94)	0.49	1.28 (0.64 - 2.6)	0.49
C	A	A	baseline	-	-	26.36 (10.84-41.88)	0.001	0.34 (0.04 -2.63)	0.3
C	A	A	1^st follow-up	0.65 (0.34-1.23)	0.18	25.93 (5.21-46.64)	0.01	0.59 (0.12 -2.82)	0.51
C	A	A	2^nd follow-up	0.5 (0.28- 0.88)	0.02	41.5 (17 - 66)	0.001	0.87 (0.18- 4.14)	0.86
C	A × examination	A	longitudinal	1.08 (0.81-1.46)	0.59	0.23 (-0.38 -0.86)	0.45	1.26 (0.69 -2.32)	0.45

Insulin degrading enzyme (IDE) haplotypes (IDE2, rs4646953; IDE7, rs2251101; IDE9, rs1887922) with frequencies > 5% were associated with Alzheimer's disease (AD), amyloid β₄₂ (Aβ₄₂) plasma levels and Type 2 diabetes mellitus (T2DM). Effect sizes and nominal p-values were derived from multivariate regression analysis with sex and presence of apolipoprotein E (APOE ε4) alleles as covariates in regressions on AD affection and Aβ₄₂ plasma level, respectively. T2DM affection as outcome used sex and BMI as covariates. Longitudinal analysis examined interactions of all covariates with the examination (baseline, 1^st and 2^nd follow-up). Associations were calculated using dominant models for AD, additive models for Aβ₄₂ plasma level and recessive models for T2DM. Nominally significant p-values (p < 0.05) are shown in bold.

ISSN: 1471-2350