Objective.—Sherpas are well-known for their physical strength at high altitudes. They adapt to high altitude so well that little acute or chronic mountain sickness has been documented in them. The possible genetic basis for this adaptation is, however, unclear. The objective of this study was to elucidate the genetic background underlying this characteristic among Sherpas with respect to the angiotension-converting enzyme (ACE) gene.

Methods.—We enrolled 105 Sherpa volunteers in Namche Bazaar (3440 meters) and 111 non-Sherpa Nepalese volunteers in Kathmandu Valley (1330 meters) in Nepal. Information about high-altitude exposure and physiological phenotypes was obtained via fieldwork investigation. The genotype of the insertion/deletion (I/D) polymorphism in the ACE gene was identified by polymerase chain reaction. Serum ACE activity was also measured.

Results.—The distribution of the I dominant genotype (II & ID) and the I allelic frequency were significantly more prevalent in Sherpas (II & ID: 94.3%, I allele: 73.3%) than in non-Sherpas (II & ID: 85.6%, P = .035; I allele: 64.0%, P = .036). Moreover, despite residing at high altitude, the circulating ACE levels of Sherpas were statistically similar to those of non-Sherpas at low altitudes (Sherpas: 14.5 ± 0.4 IU/L/37°C; non-Sherpas: 14.7 ± 0.4 IU/L/37°C; P = .755).

Conclusions.—These findings suggest that the overrepresented I allele of the ACE gene in Sherpas might be one of the fundamental genetic factors responsible for maintaining physiological low-altitude ACE activity at high altitude, which may have an advantageous physiological role in adapting to a high-altitude environment.