Table 1 Association of specific functional defects of rare MT2 variants with T2D risk.

Only rare MT2 variants (with a frequency <1%) were included. By applying Bonferroni correction, a statistically significant P value was <0.0056. A P value between 0.05 and 0.0056 was considered a trend of association (a nominal association). Nine independent association tests were performed on the basis of a T2D case-control study including 2186 individuals with T2D and 4804 controls. CI, confidence interval.

Consequences on MT2 functionRare MT2 VariantsFrequency (cases)Frequency
(controls)
Odds ratio
(95% CI)
P value
Defects in Gαi1
activation
SpontaneousA25T, A42P, L60R,
P95L, M120I/V,
S123R, V124I,
R138C/H/L, Y141F,
T201M, I223T, F250V,
Y308S, R316H
1.1%0.7%2.32 (1.17–4.60)0.016
MLT-inducedA42P, L60R, A74T,
P95L, S123R, V124I,
R138C/H/L, Y141F,
R154H, T201M,
R222H, I223T, F250V,
Y308S, R316H,
R330W, A342V
1.4%0.7%3.25 (1.73–6.10)2.4 × 10−4
Defects in Gαz
activation
SpontaneousA42P, L60R, P95L,
M120V, S123R,
R138C/H/L, T201M,
R222H, I223T, F250V,
Y308S, R316H
0.9%0.5%2.95 (1.35–6.46)0.0067
MLT-inducedA42P, L60R, A74T,
P95L, G109A,
M120I/V, S123R,
V124I, R138C/H/L,
Y141F, T201M,
R222H, I223T,
D246N, F250V,
Y308S, R316H,
R330W, A342V
1.4%0.8%2.93 (1.57–5.45)7.3 × 10−4
Defects in cAMP
inhibition
MLT-inducedA42P, L60R, P95L,
G109A, M120V,
S123R, R138C/H/L,
R222H, I223T, F250V,
Y308S, R316H,
R330W
0.9%0.6%2.83 (1.31–6.12)0.0083
Defects in β-arrestin2
recruitment
SpontaneousA42P, L60R, P95L,
G109A, S123R, V124I,
R138C/L, Y141F,
R154H, R222H, I223T,
F250V, Y308S, A342V
1.3%0.7%3.06 (1.59–5.90)8.3 × 10−4
MLT-inducedA42P, L60R, A74T,
P95L, G109A, M120V,
S123R, V124I,
R138C/H/L, L166I,
T201M, R222H,
I223T, R231H, E237K,
S238G, D246N,
F250V, Y308S,
R316H, A342V
2.7%2.3%2.13 (1.23–3.70)0.0071
Defects in ERK
activation
MLT-inducedA42P, L60R, A74T,
P95L,M120I, S123R,
V124I, R138C/H/L,
M146V, R154H,
T201M, R222H,
I223T, F250V, Y308S,
R316H
1.2%0.8%2.49 (1.29–4.80)0.0066
Neutral variantsA8S, A13V, G21S,
W22L, A25T, P36S,
A52T, A234T, I353T,
A359E
0.2%0.2%2.50 (0.59–10.59)0.21