Genetic Variation

The AAT gene is highly polymorphic. Historically, variants were characterized by gel electrophoresis of serum and initially divided into three groups according to their migration [medium (M), fast (F), and slow (S)], and, conventionally, these variants are preceded by PI. With advances in electrophoresis technology, further variants were identified based on migration characteristics in a pH 4-5 isoelectric focusing (IEF) gel. Anodal variants were assigned letters from the beginning of the alphabet. Several bands are observed on IEF, resulting from the degree of glycosylation. In a pH gradient of 4-5, AAT variants migrate as two major bands designated 4 and 6, and three minor bands 2, 7, and 8.

The migration of these bands is altered by amino acid substitutions (Fig. 2). At least four common M subtypes have been identified (designated M1-M4), with two other rare M subtypes (M5 and M6) and two common deficiency variants (designated S and Z) also arising from single-base substitutions. Other rare deficiency variants are characterized by a combination of the letter of the most closely migrating variant, and the origin of the place of the oldest living carrier. Examples of some of the variants in which the mutations have been characterized are shown in Table 1.

A mean normal plasma concentration of less than 11 mM is classified as deficient, and concentrations for the different common variants are typically in the range of 20-53 mM for MM, 18-52 mM for MS, 24-48 mM for SS, 15-42 mM for MZ, 10-23 mM for SZ, and 3.4-7.0 mM for ZZ.[2] The range of concentrations for PI ZZ falls well below this threshold, as does the very lower end of SZ, and both contribute as risk factors for disease. PI Null variants are rare, and there is considerable heterogeneity of mutations that cause them (Table 1).

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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