lec 13

• Age, sex & race


  Effects on biological function and disease in humans
• Race


  A category of humankind that shares certain distinctive physical traits
• Ethnicity


  A large group of people classed according to common racial, national, tribal, religious, linguistic or cultural origin or background
• More genetic variation within racial groups than between them
• Sex


  The biological aspects of an individual as determined by their anatomy, which is produced by their chromosomes, hormones and their interactions
• Gender


  A social construction relating to behaviours and attributes based on labels of masculinity and femininity; gender identity is a personal, internal perception of oneself and so the gender category someone identifies with may not match the sex they were assigned at birth
• Racial disparities in COVID-19 mortality
• Racial/ethnic related disparity in disease</b>
• Factors contributing to racial/ethnic disparities in disease

  • Sociodemographic, socioeconomic and health behaviour factors
  • Increased prevalence of disease risk factors
  • Inflammation - common pathophysiological pathway for numerous chronic diseases
• Highest risk of mortality from COVID-19 in the UK is for Black people
• H1N1 flu pandemic of 2009 highest risk of mortality in Pakistani ethnicity - adjusted risk ratio (RR) = 1.86 [1.39 - 2.54]; no difference in the following season
• Black and ethnic minorities are 4.5% of the English population but 21% of the NHS workforce
• Black and ethnic minorities have a poverty rate 2x that of White people
• Black and ethnic minorities are more likely to be in frontline roles
• Even when taking all these factors into account, excess risk remains unexplained
• South Asians have highest rates of comorbidities such as diabetes, hypertension and cardiovascular disease associated with severe disease and mortality from COVID-19
• Differences in virus spread due to health-seeking behaviours, intergenerational cohabitation
• Genetics, social constructs, culture identity, behavioural patterns contribute to racial/ethnic disparities in COVID-19
• Lack of diversity in training sets for artificial intelligence, e.g. US government facial recognition training set was 75% male and 85% lighter skinned people
• Sensor detects invisible light reflected from skin, but dark skin absorbs more so doesn't reflect enough to trigger
• Efforts in the industry to combat lack of diversity in AI training sets
• Vitamin D


  Link between innate immune response and vitamin D production of the anti-microbial peptide cathelicidin
• Melanin protects from overexposure and damage by UV rays
• Skin melanin content and vitamin D3 synthetic capacity inversely related, less able to support cathelicidin induction
• Might underpin infectious disease susceptibility in African versus European Americans
• Ancestry from different geographical regions, selection in pathogen rich environment - tolerate low level chronic inflammation and hyperactive response when triggered
• But in absence of high load of pathogens, innate immune profiles contribute to non-communicable disease risk
• Western environment reduces innate immune function in newly arrived versus long term Chinese immigrants
• European, African, Japanese and Latino ancestry differences in risk of atopic dermatitis
• Women more likely to have occupational skin disease, especially hand eczema
• Females more likely to develop nickel allergy at 10 - 30% versus males at 1 - 3%
• Not due to differences in intrinsic skin characteristics but different exposure patterns, women more likely to have jobs involving irritants
• 1994 EU Nickel Directive (subsumed into REACH Regulation in 2009)
• Sexual dimorphism


  Differences between biological sexes beyond sexual characteristics
• Males more susceptible to infectious diseases, females more susceptible to autoimmune disease
• Sex differences also in cancer, pain, cardiovascular disease
• Interacts with age, obesity, ethnicity, lifestyle and behavioural factors
• Sex hormones - estrogen and progesterone in females, male androgens like testosterone
• Wide variety of cell types express receptors for sex hormones, many genes have hormone response elements
• 1. linked & Y-linked gene expression