Genetic and environmental factors

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It has been demonstrated that physiological reflux, heartburn, acid regurgitation and severe GERD are more frequent in men than in women. Barrett's esophagus is in part genetically determined.24 There is much information (in adults) demonstrating the aggravating effects of alcohol, smoking, drugs, dietary components, etc. on the incidence of GER. A detailed discussion on these environmental factors is beyond the scope of this chapter. Changes in lifestyle in men and women may result in the fact that the differences in incidence in GERD between both sexes may be disappearing. With pH monitoring, we could not demonstrate a male predominance in children. All forms of GERD affect Caucasians more often than African-Americans or Native Americans (adult data).14 However, the same prevalence of troublesome infant regurgitation was found in Caucasian and Indonesian infants.27 The importance of the genetic background was hypothesized by demonstrating that esophagitis and hiatus hernia were more common in a population with the same genetic background with dyspeptic symptoms in England than in Singapore.28 Race, sex, body mass index and age were independently associated with hiatus hernia and esophagitis, race being the most important risk factor.28 However, over-the-counter use of low-dose aspirin and non-steroidal anti-inflammatory drugs has a greater impact on severe GERD, such as esophageal stricture than age.29

Carre et al described the autosomal dominant inheritance of hiatal hernia by discovering familial hiatal hernia in a large five-generation family, but without demonstrating the link to GERD.30 The genetic influence on GERD is supported by increased GER symptoms in relatives of GERD patients.31 Moreover, the concordance for GER is higher in monozygotic than dizygotic twins.32 A locus on chromosome 13q, between microsatellites D13S171 and D13S263, has been linked to severe GERD in five multiply affected families,33 but not confirmed in another five families, possibly owing to the genetic heterogeneity of GERD and the different clinical presentations of patients.34

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