Association of obesity risk SNPs in PCSK1with insulin sensitivity and proinsulin conversion

Heni, Martin; Haupt, Axel; Schäfer, Silke A; Ketterer, Caroline; Thamer, Claus; Machicao, Fausto; Stefan, Norbert; Staiger, Harald; Häring, Hans-Ulrich; Fritsche, Andreas

doi:10.1186/1471-2350-11-86

BMC Medical Genetics

Table 2 Associations of PCSK1 SNP rs6235 with anthropometrics, metabolic parameters, and proinsulin conversion

From: Association of obesity risk SNPs in PCSK1with insulin sensitivity and proinsulin conversion

SNP	rs6235 (encoding S690T)
Genotype	GG	GC	CC	β_adj ± SEM	p_dom	p_add
N (f/m)	817(537/280)	560(377/183)	108(72/36)	-	-	-
Age (years)	39 ± 1	40 ± 1	38 ± 1	-	-	-
BMI (kg/m²)	28.2 ± 0.3	28.7 ± 0.3	29.3 ± 0.8	0.016 ± 0.010	0.2	0.3
Waist circumference (cm)	92.9 ± 0.6	93.9 ± 0.7	94.9 ± 2.0	0.009 ± 0.007	0.2	0.9
Total body fat (%)	30.7 ± 0.4	31.0 ± 0.5	31.7 ± 1.0	0.014 ± 0.014	0.7	0.5
Fasting glucose (mmol/l)	5.1 ± 0.1	5.1 ± 0.1	5.1 ± 0.1	-0.004 ± 0.004	0.2	0.3
Glucose_120-min (mmol/l)	6.2 ± 0.1	6.3 ± 0.1	6.3 ± 0.2	0.005 ± 0.011	0.7	0.8
Fasting insulin (pmol/l)	61 ± 2	64 ± 2	63 ± 5	0.021 ± 0.027	0.8	0.6
Insulin sensitivity, OGTT (AU)	16.8 ± 0.4	16.4 ± 0.5	16.0 ± 0.9	-0.018 ± 0.029	0.7	0.7
Insulin sensitivity, clamp-derived (AU) (N = 512)	0.088 ± 0.003 (N = 286)	0.080 ± 0.004 (N = 191)	0.091 ± 0.009 (N = 35)	-0.023 ± 0.021	0.3	0.4
HOMA_IR (mU × mmol × l^-2)	2.4 ± 0.1	2.5 ± 0.1	2.5 ± 0.2	0.017 ± 0.029	0.9	0.6
AUC_Ins30/AUC_Glc30 (×10^-9)	40.4 ± 1.0	40.2 ± 1.3	46.0 ± 3.7	0.022 ± 0.026	0.9	0.6
First-phase insulin (pmol/l)	1247 ± 29	1251 ± 35	1383 ± 97	0.014 ± 0.024	1.0	1.0
AUC_C-Pep/AUC_Glc (×10^-9)	318 ± 3.6	316 ± 4.4	343 ± 13	0.017 ± 0.014	1.0	0.2
Proinsulin_0-min (pmol/l)	5.6 ± 0.2	5.9 ± 0.3	7.0 ± 0.9	0.081 ± 0.041	0.1	0.1
Proinsulin_30-min (pmol/l)	11.2 ± 0.3	12.2 ± 0.7	16.5 ± 2.6	0.117 ± 0.038	0.0286	0.0059
AUC_Proins (pmol/l)	34.2 ± 1.0	37.0 ± 1.5	49.1 ± 6.7	0.105 ± 0.034	0.0404	0.0018
Fasting proinsulin/fasting insulin	0.126 ± 0.004	0.129 ± 0.003	0.147 ± 0.014	0.062 ± 0.044	0.2	0.1
Proinsulin_30-min/insulin_30-min	0.036 ± 0.005	0.035 ± 0.002	0.047 ± 0.011	0.105 ± 0.041	0.0208	0.0123
AUC_Proins/AUC_Ins	0.048 ± 0.001	0.053 ± 0.003	0.068 ± 0.011	0.085 ± 0.035	0.0324	0.0090

Data represent unadjusted means ± SEM. For statistical analysis, data were ln-transformed and adjusted for gender and age. Glucose concentrations and insulin sensitivity indices were additionally adjusted for BMI. Proinsulin values as well as insulin secretion parameters were additionally adjusted for BMI and insulin sensitivity (OGTT). AUC - area under the curve; β_adj - effect sizes from the adjusted dominant model; BMI - body mass index; HOMA_IR - homeostasis model assessment-estimated insulin resistance; OGTT - oral glucose tolerance test; p_add - p-values from the additive inheritance model; p_dom - p-values from the dominant inheritance model; SNP - single nucleotide polymorphism. p-values withstanding Bonferroni correction for multiple comparisons are given in bold.

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