Background
Methods
Evolutionary analysis
Region/selection model(number of codons) | d.f. | -2ΔLnL |
Pvalue | % of sites(average dN/dS) | Selected sites |
---|---|---|---|---|---|
Loop1 (269) | |||||
M7 versus M8 | 2 | 10.04 | 0.0066 | 1.3% (1.37) | 182 (0.99, n.s.) |
M8a versus M8 | 1 | 4.87 | 0.027 | - | - |
Loop 2 N-term (251)
| |||||
M7 versus M8 | 2 | 25.86 | <0.0001 | 1.3% (1.78) | 416 (0.99, 0.99),417 (0.98, 1), 421 (0.91, 0.99) |
M8a versus M8 | 1 | 10.98 | 0.0009 | - | |
Loop 2 C-term (81)
| |||||
M7 versus M8 | 2 | <0.01 | >0.99 | - | - |
M8a versus M8 | 1 | 1.96 | 0.16 | - | |
SSD (164)
| |||||
M7 versus M8 | 2 | 5.70 | 0.058 | - | - |
M8a versus M8 | 1 | 0.02 | >0.88 | - | - |
Loop 3 (248)
| |||||
M7 versus M8 | 2 | 0.004 | >0.99 | - | - |
M8a versus M8 | 1 | 1.52 | 0.21 | - | - |
Population genetic analyses
Patients and controls
Anthropometry and DNA extraction
Results
Evolutionary analysis of NPC1 mammalian genes
Population genetics in humans
Association of NPC1 SNPs with obesity and T2D
Obese | Non-obese | |||
---|---|---|---|---|
T2D | No T2D | T2D | No T2D | |
Sample size | 441 | 379 | 203 | 445 |
Females (%) | 261 (59) | 233 (61) | 73 (36) | 216 (48.5) |
Males (%) | 180 (41) | 145 (39) | 130 (64) | 229 (51.5) |
Age ± s.d. (years) | 53.07 ± 10.61 | 42.79 ± 10.15 | 55.54 ± 16.19 | 38.56 ± 13.90 |
BMI ± s.d., kg/m2
| 35.62 ± 6.83 | 34.67 ± 3.92 | 24.25 ± 3.31 | 22.74 ± 3.3 |
Trait | Minor allele | Whole sample | Males | Females | |||
---|---|---|---|---|---|---|---|
Pvaluea
| OR (95% CI)b
|
Pvaluea
| OR (95% CI)b
|
Pvaluea
| OR (95% CI)b
| ||
Obesity
| |||||||
rs1788799 (C/G) | G (Met) | >0.5 | 1.05 (0.87 to 1.18) | >0.5 | 1.02 (0.81 to 1.27) | >0.5 | 1.02 (0.83 to 1.27) |
rs1805081 (A/G) | G (Arg) | >0.5 | 0.83 (0.78 to 1.25) | >0.5 | 1.06 (0.76 to 1.47) | >0.5 | 0.93 (0.67 to 1.30 |
BMI
|
P
value
a
|
BETA
c
|
P
value
a
|
BETA
c
|
P
value
a
|
BETA
c
| |
rs1788799 (C/G) | G (Met) | 0.462 | 0.328 | >0.5 | 0.490 | >0.5 | 0.231 |
rs1805081 (A/G) | G (Arg) | >0.5 | -0.411 | >0.5 | -0.343 | >0.5 | -0.450 |
T2D
|
P
value
a
|
OR (95% CI)
b
|
P
value
a
|
OR (95% CI)
b
|
P
value
a
|
OR (95% CI)
b
| |
rs1788799 (C/G) | G (Met) |
0.027
| 1.24 (1.05 to 1.48) |
0.004
| 1.50 (1.15 to 1.95) | >0.5 | 1.07 (0.85 to 1.36) |
rs1805081 (A/G) | G (Arg) | >0.5 | 1.06 (0.82 to 1.39) | >0.5 | 1.11 (0.76 to .60) | >0.5 | 1.04 (0.71 to 1.52) |
Trait | Haplotype
(rs1805081 -rs1788799, residues)
| Whole sample | Males | Females | |||
---|---|---|---|---|---|---|---|
Freq.a
|
Pvalue (OR) | Freq.a
|
Pvalue (OR) | Freq.a
|
Pvalue (OR) | ||
T2D (all) | |||||||
GC (Arg-Ile) | 0.12 | 0.451 (1.11) | 0.12 | 0.495 (1.14) | 0.12 | 0.653 (1.09) | |
AG (His-Met) | 0.41 |
0.009 (1.26) | 0.40 |
0.0012 (1.54)
| 0.41 | 0.545 (1.08) | |
AC (His-Ile) | 0.47 |
0.003 (0.77) | 0.48 |
0.0004 (0.63)
| 0.47 | 0.425 (0.91) | |
T2D (obese) | |||||||
GC (Arg-Ile) | 0.12 | 0.577 (1.10) | 0.12 | 0.498 (1.20) | 0.12 | 0.780 (1.07) | |
AG (His-Met) | 0.42 | 0.230 (1.14) | 0.42 |
0.013 (1.44) | 0.41 | 0.745 (0.95) | |
AC (His-Ile) | 0.46 | 0.142 (0.85) | 0.46 |
0.004 (0.60) | 0.47 | 0.813 (1.03) | |
T2D (non-obese) | |||||||
GC (Arg-Ile) | 0.11 | 0.77 (1.07) | 0.11 | 0.957 (1.02) | 0.12 | 0.666 (1.19) | |
AG (His-Met) | 0.40 |
0.0125 (1.46) | 0.40 |
0.033 (1.52) | 0.41 | 0.158 (1.40) | |
AC (His-Ile) | 0.49 |
0.009 (0.67) | 0.49 |
0.042 (0.69) | 0.47 | 0.088 (0.65) |
Trait | Haplotype
(rs1805081-rs1788799, residues)
| Whole sample | Males | Females | |||
---|---|---|---|---|---|---|---|
BETAa
|
Pvalue | BETAa
|
Pvalue | BETAa
|
Pvalue | ||
HDL-cholesterol | |||||||
GC (Arg-Ile) | -0.047 |
0.026
| -0.070 |
0.017
| -0.020 | 0.698 | |
AG (His-Met) | -0.013 | 0.32 | 0.004 | 0.803 | -0.0278 |
0.048
| |
AC (His-Ile) | 0.032 |
0.015
| 0.025 | 0.190 | 0.040 |
0.023
| |
LDL-cholesterol | |||||||
GC (Arg-Ile) | -0.068 | 0.650 | -0.140 | 0.477 | -0.034 | 0.877 | |
AG (His-Met) | 0.149 | 0.124 | -0.125 | 0.330 | 0.200 | 0.157 | |
AC (His-Ile) | -0.105 | 0.265 | -0.701 | 0.583 | -0.144 | 0.289 | |
Total cholesterol | |||||||
GC (Arg-Ile) | -0.011 | 0.408 | 0.003 | 0.872 | -0.028 | 0.166 | |
AG (His-Met) | 0.010 | 0.224 | 0.002 | 0.873 | 0.022 | 0.097 | |
AC (His-Ile) | -0.005 | 0.538 | -0.003 | 0.794 | -0.008 | 0.505 | |
Triglycerides | |||||||
GC (Arg-Ile) | 0.045 | 0.101 | 0.104 |
0.003
| -0.0313 | 0.466 | |
AG (His-Met) | 0.024 | 0.173 | -0.014 | 0.563 | 0.071 |
0.009
| |
AC (His-Ile) | -0.041 |
0.018
| -0.031 | 0.181 | -0.052 |
0.046
|