APOE – a genetic marker of comorbidity in subjects with morbid obesity

Abstract

Background: In population-based studies, the genetic variability of the APOE E alleles have been associated with health outcomes. Health problems are common in subjects with obesity. This study explored associations between the APOE E alleles and comorbidity in subjects with morbid obesity. Methods: The study included consecutive subjects referred for evaluation of bariatric surgery with morbid obesity (defined as BMI > 40 or > 35 kg/m 2 with complications related to obesity). The subjects followed a conservative weight loss program for 6 months before surgery and had a follow-up visit 12 months after surgery. Demographic data and a set psychosomatic scores (musculoskeletal pain, WHO-5 Well-Being Index, Rosenberg Self-Esteem Scale, Hopkins Symptom Checklist 10; Epworth Sleepiness Scale, and Fatigue Severity Scale) were collected, and blood samples were analysed for haematological and biochemical parameters and APOE alleles. Results: One hundred and forty subjects (men/women: 32 (23%)/108 (77%) with mean age 43.0 (SD 8.7) years and BMI 42.1 (SD 3.8) kg/m 2 were included. One hundred and eight and 92 subjects had data after conservative treatment and 12 months after surgery, respectively. The prevalence of the APOE alleles were: E2E2: 1 (0.7%), E2E3: 13 (9.3%), E2E4: 4 (2.9%), E3E3: 71 (50.7%), E3E4: 47 (33.6%), and E4E4: 4 (2.9%). The prevalence rates were as anticipated in a Norwegian population. The weight loss during conservative treatment and after bariatric surgery was independent of E allele variability. E2 was associated with a significant or clear trend toward improvement of all psychosomatic disorders. There was a significant fall in CRP during the two treatment periods with weight loss. E2 and E4 were significantly associated with high and low CRP, respectively, but no associations were seen between CRP and comorbidity. Conclusions: The most marked finding was the association between E2 and improvement of all psychosomatic disorders. The positive and negative associations between CRP and E2 and E4, respectively, could indicate effects on inflammation and immunological reactions.

Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets

“…Consistent with quantile-dependent expressivity and the higher CRP concentrations of obese subjects, Friedlander et al (2006) reported that the heritability of untransformed CRP was nearly three-fold greater in obese than nonobese subjects (0.670 vs. 0.256). In addition, data reported by Farup, Rootwelt & Hestad (2020) showed that the CRP difference between non-carriers and carriers of the APOE ε4-allele decreased linearly as average CRP concentrations decreased in morbidly obese patients undergoing weight loss ( Fig. 3A ).…”

“… Simple regression analysis of showing larger genotype differences associated with higher estimated average CRP response for the data presented in: (A) Farup, Rootwelt & Hestad (2020) report on the APOE CRP differences (non-carriers minus carriers of ε4-allele) in morbidly obese patients losing weight; (B) Perry et al (2009) report on the rs3091244 CRP difference (T-allele carrier minus noncarrier) post CABG surgery ( P linear = 0.08); (C) Perry et al (2009) report on the rs1800947 CRP difference (GG homozygotes minus C-allele carrier) post CABG surgery ( P linear = 0.11); (D) Brull et al (2003) report on the rs1130864 CRP difference (TT homozygotes minus C-allele carriers) pre- and post CABG surgery ( P linear = 0.02); (E) D’Aiuto et al (2005) report on the rs1130864 CRP difference (TT homozygotes minus C-allele carriers) following periodontal intensive therapy ( P linear = 0.002); (F) Motoyama et al (2009) report on the rs1800947 CRP difference (GG homozygotes minus C-allele carriers) following esophagectomy surgery ( P linear = 0.07). …”

Increased ApoE Expression in Follicular Fluid and the ApoE Genotype Are Associated With Endometriosis in Chinese Women

“…Most studies on ApoE have focused on cardiovascular disease and Alzheimer's disease risks due to its role related to lipids (21). However, the effects of ApoE go far beyond these diseases because this protein can affect a number of diseases, such as fertility, diabetes, and obesity (22)(23)(24).…”

Gene polymorphisms associated with lipid metabolism disorders in young adults with risk of ­sudden cardiac death

“…В развитие дислипидемии значительный вклад вносят генетические полиморфизмы различных генов, ответственных за обмен липидов в организме. К наиболее изученным генам и полиморфизмам в них относят следующие: полиморфизм Leu28Pro (rs 429358) в гене APOE, полиморфизм C3238G (rs 5128) в гене APOC3, полиморфизм Gln192Arg (rs 662) в гене PON1, полиморфизм Ser447Ter (rs 328) в гене LPL и полиморфизм G250A (rs 1800588) в гене LIPC [7][8][9][10][11][12][13][14][15][16][17].…”

“…Известно несколько полиморфных вариантов гена АРОЕ, одному из которых -Leu28Pro (rs 429358), помимо влияния на липидный обмен через изменение структуры молекулы APO E, нарушения механизма липидного обмена и потенцирования гиперлипопротеинемии, приписывают взаимосвязь с развитием ожирения. Традиционно к варианту риска относится носительство минорного аллеля T в данном полиморфизме [7,8,18]. APO C3 играет ключевую роль в метаболизме триглицеридов.…”