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

BMC Medical Genetics

Table 1 Association results of insulin degrading enzyme SNPs

		AD		Aβ₄₂plasma level [pg/ml]		T2DM
Polymorphism (major/minor allele)	focus	OR (95% CI)	p-value	slope (95% CI)	p-value	OR (95% CI)	p-value
IDE2 (T/C)	baseline	-	-	22.36 (8.08 - 36.6)	0.002	0.82 (0.23 - 2.86)	0.75
IDE2 (T/C)	1^st follow-up	0.66 (0.36 - 1.21)	0.18	21.04 (2.08 - 40)	0.03	0.96 (0.3 - 3.05)	0.95
IDE2 (T/C)	2^nd follow-up	0.55 (0.32 - 0.95)	0.03	35.26 (12.8 -57.8)	0.002	1.32 (0.41 - 4.24)	0.64
IDE2 (T/C) × examination	longitudinal	1.13 (0.84 - 1.43)	0.41	8.23 (1.93 -14.5)	0.01	1.27 (0.81 - 1.73)	0.31
IDE7 (A/G)	baseline	1.74 (0.63 - 4.78)	0.28	-5.24 (-16.7 - 6.2)	0.37	2.4 (1.25 - 4.63)	0.009
IDE7 (A/G)	1^st follow-up	1.26 (0.77 - 2.07)	0.35	-5.31 (-21 -10.3)	0.51	2.62 (1.32 - 5.18)	0.006
IDE7 (A/G)	2^nd follow-up	0.97 (0.62 - 1.52)	0.89	-14.27 (-33.7 - 5.2)	0.15	3.47 (1.72 - 6.97)	0.0005
IDE7 (A/G) × examination	longitudinal	0.86 (0.56 - 1.16)	0.33	-3.37 (-8.2 - 1.49)	0.18	1.1 (0.91 - 1.3)	0.32
IDE9 (A/G)	baseline	1.87 (0.71 - 4.92)	0.21	-7.36 (-19.5 - 4.8)	0.24	1.65 (0.72 - 3.79)	0.24
IDE9 (A/G)	1^st follow-up	1.02 (0.62 - 1.69)	0.94	-8.39 (-24.9 - 8.1)	0.32	1.17 (0.46 - 3.0)	0.75
IDE9 (A/G)	2^nd follow-up	0.99 (0.62 - 1.58)	0.96	-11.1 (-31.8 - 9.7)	0.3	1.75 (0.7 - 4.37)	0.23
IDE9 (A/G)× examination	longitudinal	0.88 (0.57 - 1.19)	0.42	-0.85 (-5.5 - 3.83)	0.72	0.98 (0.78- 1.17)	0.81

Insulin degrading enzyme (IDE) SNPs (IDE2, rs4646953; IDE7, rs2251101; IDE9, rs1887922) 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