Table3.
Associations of 13 tag SNPs in PFKFB2 with insulin secretion, insulin sensitivity, T2D and DN in AI
| SNP | Location | R/N | RAF | AIR n = 298 full-heritage |
30-min insulin n = 298 full-heritage |
Insulin sensitivity n = 555 |
T2D n = 3625*/7710£/10816§ |
DN n = 1610*/2452£/3316§ |
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Beta | P | Beta | P | Beta | P | OR (95% CI) | P | OR (95% CI) | P | ||||
| rs78357410* | 5′flanking | T/C | 0.05 | 0.96 | 0.67 | 1.02 | 0.74 | 1.06 | 0.06 | 0.94 (0.72–1.23) | 0.68 | 0.88 (0.56–1.37) | 0.56 |
| rs79168343£ | 5′flanking | C/T | 0.94 | 1.05 | 0.67 | 0.95 | 0.72 | 0.99 | 0.85 | 0.86 (0.72–1.03) | 0.11 | 0.89 (0.67–1.19) | 0.44 |
| rs12032074* | 5′flanking | A/G | 0.85 | 0.94 | 0.42 | 1.03 | 0.67 | 1.00 | 0.84 | 1.09 (0.93–1.27) | 0.31 | 0.95 (0.75–1.22) | 0.71 |
| rs2243816£ | intron | T/C | 0.22 | 0.98 | 0.89 | 0.95 | 0.47 | 1.00 | 0.82 | 0.99 (0.89–1.10) | 0.84 | 1.10 (0.91–1.33) | 0.33 |
| rs11120137§ | intron | T/C | 0.11 | 0.81 | 0.03 | 0.78 | 3.0 × 10−5 | 0.97 | 0.17 | 1.04 (0.94–1.15) | 0.49 | 1.42 (1.16–1.73) | 5.1 × 10−4 |
| rs77757597£ | 3′UTR | G/T | 0.65 | 0.95 | 0.34 | 0.98 | 0.46 | 1.00 | 0.83 | 1.01 (0.89–1.15) | 0.83 | 1.07 (0.87–1.31) | 0.51 |
| chr1:207250175* | 3′UTR | T/C | 0.04 | 1.09 | 0.37 | 1.02 | 0.76 | 1.04 | 0.20 | 0.82 (0.62–1.10) | 0.18 | 0.63 (0.38–1.03) | 0.07 |
| rs1060286£ | 3′UTR | G/A | 0.01 | 1.14 (0.88–1.48) | 0.32 | 0.90 (0.46–1.77) | 0.76 | ||||||
| rs17258746§ | 3′UTR | A/T | 0.10 | 0.78 | 0.03 | 0.78 | 1.1 × 10−4 | 0.98 | 0.31 | 1.05 (0.94–1.18) | 0.37 | 1.64 (1.32–2.02) | 5.8 × 10−6 |
| rs3748672£ | 3′UTR | A/G | 0.01 | 1.08 (0.87–1.33) | 0.50 | 0.71 (0.42–1.20) | 0.21 | ||||||
| rs6673422£ | 3′UTR | G/A | 0.12 | 0.83 | 0.04 | 0.79 | 1.0 × 10−4 | 0.99 | 0.50 | 1.10 (0.96–1.25) | 0.17 | 1.33 (1.05–1.68) | 0.02 |
| chr1:207260089* | 3′flanking | T/C | 0.91 | 0.98 | 0.82 | 1.00 | 0.98 | 1.00 | 0.85 | 1.10 (0.89–1.35) | 0.38 | 1.12 (0.79–1.59) | 0.51 |
| rs56009508* | 3′flanking | A/C | 0.84 | 0.98 | 0.66 | 0.93 | 0.24 | 0.99 | 0.46 | 1.02 (0.88–1.20) | 0.77 | 1.04 (0.80–1.35) | 0.76 |
*SNPs (n = 5) analyzed in full-heritage Pima Indians (n = 3625 for T2D; n = 1610 for DN); £: SNPs (n = 6) analyzed in combined samples of full-heritage Pima Indians and mixed-heritage AI (n = 7710 for T2D; n = 2452 for DN); §: SNPs (n = 2) analyzed in combined samples of full-heritage, mixed-heritage and a replication sample of urban AI (n = 10816 for T2D; n = 3316 for DN). SNPs (rs1060286 and rs3748672) have mAF = 0.01, and are too rare to analyze traits for AIR, 30-min plasma insulin and insulin sensitivity (measured by the rate of glucose disappearance during insulin-stimulation). The risk allele (given first) is defined as the allele with a higher risk for BMI; ORs for T2D or DN are given per copy of this allele. R: risk allele; N: non-risk allele; RAF: risk allele frequency. AIR, 30-min plasma insulin concentrations and insulin sensitivity are log10-transformed before analyses to approximate a normal distribution, and beta is exponentiated to obtain the effect per copy of the risk allele, expressed as a multiplier. Beta and P value for AIR are adjusted for age, sex, % body fat and rate of glucose disappearance during insulin-stimulation. Beta and P value for 30-min plasma insulin concentrations are additionally adjusted for 30-min plasma glucose concentrations during an OGTT. Beta and P value for insulin sensitivity are adjusted for age, sex, % body fat and heritage. Beta and P values for T2D are adjusted for age, sex, birth-year and heritage. Beta and p for DN are adjusted for duration of diabetes, sex and heritage. Bold values: P < 0.05.