Document Type

Journal Article

Publication Date






Skin fluorescence (SF) is a non-invasive marker of AGEs and is associated with the long-term complications of diabetes. SF increases with age and is also greater among individuals with diabetes. A familial correlation of SF suggests that genetics may play a role. We therefore performed parallel genome-wide association studies of SF in two cohorts.


Cohort 1 included 1,082 participants, 35–67 years of age with type 1 diabetes. Cohort 2 included 8,721 participants without diabetes, aged 18–90 years.


rs1495741 was significantly associated with SF in Cohort 1 (p < 6 × 10−10), which is known to tag theNAT2 acetylator phenotype. The fast acetylator genotype was associated with lower SF, explaining up to 15% of the variance. In Cohort 2, the top signal associated with SF (p = 8.3 × 10−42) was rs4921914, also in NAT2, 440 bases upstream of rs1495741 (linkage disequilibrium r 2 = 1.0 for rs4921914 with rs1495741). We replicated these results in two additional cohorts, one with and one without type 1 diabetes. Finally, to understand which compounds are contributing to the NAT2–SF signal, we examined 11 compounds assayed from skin biopsies (n = 198): the fast acetylator genotype was associated with lower levels of the AGEs hydroimidazolones of glyoxal (p = 0.017).


We identified a robust association between NAT2 and SF in people with and without diabetes. Our findings provide proof of principle that genetic variation contributes to interindividual SF and thatNAT2 acetylation status plays a major role.


Reproduced with permission of Springer, Diabetologia.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

Peer Reviewed


Open Access


ESM Study writing groups.pdf (27 kB)
ESM Study writing groups

ESM Table 1.pdf (179 kB)
ESM Table 1

ESM Table 2.pdf (167 kB)
ESM Table 2

ESM Table 3.pdf (174 kB)
ESM Table 3

ESM Table 4.pdf (102 kB)
ESM Table 4

ESM Table 5.pdf (87 kB)
ESM Table 5

ESM Table 6.pdf (219 kB)
ESM Table 6

ESM Table 7.pdf (210 kB)
ESM Table 7

ESM Table 8.pdf (100 kB)
ESM Table 8

ESM Table 9.pdf (155 kB)
ESM Table 9

ESM Table 10.pdf (96 kB)
ESM Table 10

ESM Fig. 1.pdf (384 kB)
ESM Fig. 1

ESM Fig. 2.pdf (26 kB)
ESM Fig. 2

ESM Fig. 3.pdf (258 kB)
ESM Fig. 3

ESM Fig. 4.pdf (785 kB)
ESM Fig. 4

ESM Fig. 5.pdf (785 kB)
ESM Fig. 5

ESM Fig. 6.pdf (120 kB)
ESM Fig. 6

ESM Fig. 7.pdf (861 kB)
ESM Fig. 7

ESM Fig. 8.pdf (284 kB)
ESM Fig. 8