Endocrine Abstracts

Background: As persistant organic pollutants, polychlorinated biphenyls (PCBs) are widespread in environment worldwide. Serum PCBs and nuclear factor erythroid 2-related factor 2 (NRF2) are associated with glucose homeostasis damage in the general population. However, there is a lack of epidemiological evidence on the interaction between serum PCBs and NRF2 gene in relation to glucose homeostasis damage.

Objectives: We aimed to explore the interaction effects of PCB exposure and NRF2 genetic polymorphisms on glucose homeostasis through a longitudinal epidemiological study.

Methods: A total of 1705 participants with 6 years follow-up from the Wuhan-Zhuhai prospective cohort was included. Repeated fasting plasma glucose (FPG) and insulin (FPI), and serum PCBs were measured for each participant. The genotypes were determined using the Infinium OmniZhongHua-8 BeadChip and 39 single nucleotide polymorphisms within the NRF2 gene were included. Generalized linear models were used to analyze the relationships of serum PCBs and NRF2 genetic polymorphisms with glucose homeostasis indices over 6 years.

Results: NRF2 genetic polymorphisms (rs1806649, rs62173695, rs34468415, rs117045674, rs141429955, and rs117263449) were significantly associated with changes in glucose homeostasis indices over 6 years. Furthermore, we observed significant interactions between NRF2 genetic polymorphisms and PCBs on changes in glucose homeostasis indices over 6 years (P interaction<0.05), especially rs117263449 and rs141429955. Each 1-unit increase in ln-transformed PCB-118 was associated with a 0.472 increment of FPG over 6 years among rs117263449 TT/TC genotype; and a 1.898 mmol/l, 47.894 mU/l, and 20.571 increment of FPG, FPI, and homeostasis model assessment of insulin resistance (HOMA-IR) over 6 years among rs141429955 AG genotype, respectively. Each 1-unit increase in ln-transformed PCB-52 and PCB-101 was associated with a 5.862 and 15.325 mU/l increment of FPI, and a 2.634 and 6.518 increment of HOMA-IR among rs117263449 TT/TC genotype, respectively. Each 1-unit increase in ln-transformed PCB-52 and PCB-101 was associated with a 27.386 and 60.361 mU/l increment of FPI, and a 11.849 and 25.636 increment of HOMA-IR among rs141429955 AG genotype, respectively.

Conclusions: The NRF2 gene might modify the longitudinal relationships between PCB exposure and glucose homeostasis damage among Chinese general adults. Our results suggested that redox-related NRF2 gene should be more considered to prevent glucose homeostasis damage, especially among individuals with high PCB exposure. More mechanistic studies are warranted.